Current Issue PDF - Vanderbilt-Ingram Cancer Center

momen um
Moving toward a future without cancer.
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s p r i n g
IN THIS ISSUE: CANCER 2.0 SOCIAL MEDIA SOWING THE SEEDS OF INNOVATION
Gut reaction
Understanding how infection causes
stomach cancer could lead to new
treatments, prevention

On the cover:
Spiral-shaped Helicobacter pylori bacteria (red), shown here on
the surface of the human stomach, colonize the stomach lining.
Infection with H. pylori is associated with gastritis (stomach
inflammation), stomach ulcers and gastric cancer. (See page 8)
Image by Science Photo library
EDITOR
Melissa Marino
CONTRIBUTING WRITERS
Michelle Eckland, Paul Govern, Leigh MacMillan, Cynthia
Floyd Manley, Melissa Marino, Jessica Pasley, Dagny Stuart
PHOTOGRAPHY/ILLUSTRATION
Mary Donaldson, Joe Howell, Anne Rayner, Susan Urmy
DESIGN & ART DIRECTION
Diana Duren
VICC ASSOCIATE DIRECTOR FOR COMMUNICATIONS
Cynthia Floyd Manley
DIRECTOR OF PUBLICATIONS
Nancy Humphrey
EXECUTIVE DIRECTOR OF NEW MEDIA
AND ELECTRONIC PUBLICATIONS
Wayne Wood
COVER PHOTO
Science Photo Library
EDITORIAL OFFICE
Vanderbilt University Medical Center
Office of News and Public Affairs
D-3237A Medical Center North
Nashville, TN 37232-2390
(615) 322-4747
CONNECT WITH US
on Twitter: www.twitter.com/ManleyatVICC
and Facebook: www.facebook.com/vanderbiltingram
EDITORIAL BOARD
Felice Apolinsky, L.C.S.W., Jill Austin, MBA, Dan Beauchamp,
M.D., Greg Burns, Carol Eck, R.N., MBA, Deb Friedman, M.D.,,
Laura Goff, M.D., Scott Hiebert, Ph.D., Orrin Ingram, Beth
Jones, M.A., Teresa Knoop M.S.N., R.N., Mark Magnuson, M.D.,
Arnold Malcolm, M.D., Jennifer Pietenpol, Ph.D., Barbara
Presogna, Cindy Seay, Anne Enright Shepherd, M.A., Anne
Washburn, M.P.H., Elizabeth Williams, Ph.D.
Celebrating survivors
Today, a cancer diagnosis is no longer a death sentence. Thanks to
advances in research and treatment, more than 11 million Americans
today are living with and beyond cancer. Each spring, Vanderbilt-
Ingram Cancer Center hosts a “Celebration of Cancer Survivorship,” a
free event for everyone affected by cancer – survivors, caregivers,
family and friends, and health and research professionals.
(Photos by Susan Urmy)
web link
To see highlights of the 2010 event, please visit: www.vicc.org/momentum.
Momentum is published twice a year by
Vanderbilt-Ingram Cancer Center, in cooperation
with the Vanderbilt University Medical Center
Office of News and Communications. The editor welcomes
letters and comments from readers at the above address.
Vanderbilt University is committed
to principles of equal opportunity and
affirmative action.
© 2009 Vanderbilt University
momentum
Moving toward a future without cancer.

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contents
s p r i n g
01
04
32
08
20
f e a t u r e s
08 GUT REACTION
Helicobacter pylori, a curvy little
bacterium implicated in stomach
cancer, may offer clues about how
“germs” are involved in cancer
development – and how human
genetics and environment interact
to initiate cancer.
16 SOWING THE SEEDS OF
INNOVATION
“Stimulus” grants are supporting
projects ranging from the development
of animal models of rare cancers
to cancer drug development
and the training of the next generation
of cancer researchers.
20 CANCER 2.0
Decreasing costs and improved technologies
for probing the human
genome have led to an explosion of
new genetic information. Vanderbilt
biomedical informatics faculty are
using the power of computers to
make sense of this mountain of
data and find ways to use it to
improve care.
28 A CLICK AWAY
Social media – through platforms
like blogs, Facebook and Twitter – is
helping build communities of cancer
survivors, their friends and families,
and health care professionals and
advocates.
d e p a r t m e n t s
02 DIRECTOR’S LETTER
A word from Jennifer Pietenpol,
Ph.D., director of Vanderbilt-Ingram
Cancer Center.
03 A CLOSER LOOK
A change in career direction during
college led Karen Munyon to radiation
therapy – and to her current
position managing Vanderbilt-
Ingram’s radiation oncology clinics.
04 SPOTLIGHT ON KIDNEY CANCER
What Jeff Kidwell thought was simple
back pain turned out to be a 17-
centimeter kidney tumor. After four
years of battling the disease, he is
getting back to the things he loves:
golf, UT games, and his family.
32 STORIES OF SURVIVAL
Michelle Eckland, who lost her
mother to a rare cancer just weeks
before leaving for college, writes
about dealing with the loss of a parent
– and about helping another
cancer survivor realize his dream.
37 QUICK TAKES
News from around the Cancer
Center
40 JOURNAL WATCH
Highlights of recent publications by
Vanderbilt-Ingram researchers
web link
To view Momentum online:
www.vicc.org/momentum
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D I R E C T O R ’ S L E T T E R
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Director’s letter
J O E H O W E LL
With or without
the stimulus
funding,
Vanderbilt-
Ingram
researchers are
attacking cancer
from all angles.
Whether through job losses, workplace budget cuts, or just tightening the belt at
home, we’ve all been affected by the economic downturn.
Here at Vanderbilt-Ingram Cancer Center, we have not let the economy stall our
progress. We took very seriously the once-in-a-lifetime opportunity afforded by the
American Recovery and Reinvestment Act and were successful in securing more than $40
million in “stimulus” grants.
These funds from the National Cancer Institute and other divisions of the National
Institutes of Health will allow our researchers to enhance their existing research projects
and to pursue new areas of high impact cancer research.
In this issue of Momentum, we present a sample of research being fueled by “stimulus”
grants – from generating animal models of rare cancers to developing drugs to treat a particularly
lethal form of breast cancer.
This funding supports almost every area of cancer research: basic molecular mechanisms
that cause cancer to form; novel methods of detection and therapeutic monitoring; and the
training of new young investigators.
By some estimates, each dollar awarded through NCI grants returns two dollars to the local economy.
But in addition to realization of any economic benefit, we know that this additional funding will enrich
our knowledge about cancer. The stimulus funding will place our investigators in a stronger position to
obtain longer-term federal grants as well as philanthropic and foundational support to continue the
“momentum” they are building today.
With or without the stimulus funding, Vanderbilt-Ingram researchers are attacking cancer from all
angles. Among them:
• We have an incredibly strong group of researchers investigating the role of an infectious organism
– a curvy little bacterium called Helicobacter pylori – in stomach cancer, the second leading cause of
cancer mortality globally. Though their research focuses on one type of bacteria, it offers clues about
how pathogenic organisms are involved in cancers – and how human genetics and environment interact
to initiate cancer development.
• With decreasing costs and improved technologies for studying the human genome, there has
been an explosion of new genetic information. At Vanderbilt, we are fortunate to have the nation’s
largest biomedical informatics faculty – some of them trained oncologists – to help make sense of this
mountain of data and find ways to use it to improve care. In this issue, we introduce you to some of
these investigators and their important work.
• Technology is also impacting the cancer community by enabling the existence of online communities
of survivors, their friends and families, and health care professionals and advocates. Social media platforms
like Facebook and Twitter are bringing these communities together. In this issue, you’ll learn how
these communities can benefit survivors and how Vanderbilt-Ingram is part of this new phenomenon.
As always, we bring you stories about our researchers, clinicians, educators – and survivors – that
keep propelling us forward toward a “world without cancer.”
We’re making progress. Let’s keep up the “momentum.”
Sincerely,
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A C L O S E R L O O K
ACLOSERLOOK
KAREN MUNYON
Manager, Radiation Oncology Centers
03
KAREN MUNYON, MBA, BSRT, GREW UP THINKING SHE WAS GOING TO BE A PHARMACIST;
she was a pre-pharmacy major, had worked in a pharmacy, and had relatives in the field.
But the year she applied to the pharmacy program, there were only 60 slots available and
she was placed on the alternate list.
Unsure of her options, she went in search of “something in the medical field” that
matched her interests and course work. Then she visited the basement of the College of
Allied Health at the University of Oklahoma, where she was introduced to the world of
radiation therapy – the medical use of radiation to treat cancer – and she has never
looked back.
“The moment I saw the radiation therapy program, I knew it was what I wanted
to do,” said Munyon. “It had lots of computer and high tech applications. Something
just clicked in me.
“It was almost like an act of God – the door opened, and I went right through it.”
Munyon graduated from the University of Oklahoma in 1991 with a degree in
radiologic technology and later received her MBA from Oklahoma City University in
1994. She joined Vanderbilt in 1997 as a radiation therapist. After five years in that
role, she was asked to lead the project to build and manage Vanderbilt-Ingram Cancer
Center’s satellite radiation oncology centers.
Now Munyon is the manager of the Vanderbilt-Ingram Cancer Center at Franklin
and Gateway-Vanderbilt Cancer Treatment Center in Clarksville.
At first, her parents were not sure of her new career direction.
“I’m a real softy,” she admitted. “And my parents didn’t think I would be able to handle
the population of patients and deal with this kind of work. And it can be really hard.
S U SAN U R M Y
“You build a rapport with your patients
and families. You see the same patient every
day for two to eight weeks. You really get to
know them. The hardest days are when you
lose a patient.”
Some of the most heart-warming experiences
involved pediatric patients.
“When you treat a child, they are so
trusting and accepting, and there is no fear of
dying,” she said. “They are always positive
and smiling.”
Even though Munyon is no longer actively
treating patients, she is still very much involved
with their care. In her role as manager, she
handles the patient satisfaction surveys.
“It’s what keeps me coming back to work
every day,” said Munyon. “People are so thankful
and appreciative. They are so grateful for the
things we do for them. Even if we can’t cure
them, they know we are here to help them.
“I may not be the one treating them, but
getting that feedback, it gives me a sense that
I’m doing a good job when someone is happy
with their care. It is a reflection of the center
as a whole.”
Munyon’s impact extends beyond the
centers as well. She has been very involved in
the local Relay for Life in Williamson
County, and the Center has stepped up to be
a presenting sponsor of this year’s American
Cancer Society event in June.
“Karen is a great ambassador for
Vanderbilt-Ingram with our patients and with
neighbors of our outlying centers,” said
Cynthia Manley, associate director for
Communications at Vanderbilt-Ingram. “She
is very dedicated to making sure that we are
truly a part of the communities we serve.”
One of Munyon’s greatest joys is meeting
a person who was treated in one of the satellite
facilities and hearing they had a positive
experience.
“To know that you gave a person one
more day with someone they love or care
about is such a satisfying feeling. I really do
love my job.”
– by Jessica Pasley
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04
SPOTLIGHT:KIDNEY CANCER
Up to par
KIDNEY CANCER SURVIVOR GETS BACK ON COURSE
On April 17, 2006, Jeff Kidwell bent over to pick up a 5-gallon paint
bucket and felt a stabbing pain in his back. The residential contractor
shook it off — pains like that seem to come with the job. That evening
there was blood in his urine. Still, he wasn’t concerned.
At 5 o’clock the next morning, excruciating pain “like someone was kicking me constantly” propelled
Kidwell to the local hospital emergency room. The doctor ordered a CT scan and then had to
deliver some hard news.
“He told me I had a mass on my kidney, about 17 centimeters in size and it was called kidney
cancer,” recalled Kidwell.
It was a shocking diagnosis. Kidwell was just 42…a husband and father of three sons.
Energetic, plain-spoken and athletic, he exudes a can-do attitude. He refereed high school football
games for nearly two decades and coached his middle son’s baseball team – all while serving as the
Building Official and Zoning Officer for the city of Clinton, Tenn. Eventually, the avid golfer and
University of Tennessee sports fan became a residential contractor. He never seemed to stop moving.
But the diagnosis of kidney cancer would trigger a marathon test of his endurance and his
capacity to take risks.
“To be honest, I only really felt sorry for myself one day and that was the very first day,” said
Kidwell. “At that point, I drew a line in the sand and said, ‘I’m going after this.’ Whatever it takes,
however long it takes, I’m going to do whatever I need to do. The fight is on.”
Kidwell had no idea how difficult or lengthy the fight would be. While kidney cancer (also known
as renal cell cancer), isn’t common, it is often lethal. The American Cancer Society estimates 57,760
Americans are diagnosed annually and 12,980 die from the disease. The number of cases is climbing.
Many kidney tumors are found by accident, when the patient has a scan for something else. Because so
many patients are getting sophisticated CT scans or MRIs these days, more tumors are being discovered
before symptoms arise. Tobacco smoking and the increase in obesity also may contribute to the
rising number of renal cell cancer cases.
Kidwell had none of the known risk factors, which also include family history of the disease and
exposure to chemicals like industrial solvents. What Kidwell did have was a very large tumor and a
local urologist who referred him to Vanderbilt-Ingram Cancer Center in Nashville, where Kidwell
decided to launch his battle against cancer.
Michael Cookson, M.D., Patricia and Rodes Hart Professor of Urologic Surgery at Vanderbilt-
Ingram, told Kidwell the tumor was encapsulated, so the entire kidney had to be removed. Would
that be enough for a cure? Additional scans revealed a spot on one of Kidwell’s lungs – evidence the
cancer might be spreading.
B y D a g n y S t u a r t
| P h o t o g r a p h y b y J o e H o w e l l
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Kidwell’s doctors suggested a clinical trial of a new drug, and
he didn’t hesitate to sign up.
“Clinical trials are the right thing to do,” explained Kidwell.
“I’m the first in line because, if it helps me, it’s going to benefit
someone else down the line. If there is a clinical trial in one of my
doctors’ areas, I’ll sign on because that’s how they get the data and
the research.”
The fact that there were new investigational drugs to try is evidence
of advances in treatment for renal cell cancer. Previously the
only option was surgical removal of the tumor. For patients with
localized early-stage disease, surgery sometimes can provide a cure.
But all too often, patients are at high risk for a recurrence, and
unlike breast cancer or colon cancer, there is no standard adjuvant
therapy for renal cell cancer.
“What has made it so difficult to treat over the years has been
its resistance to common therapy like chemotherapy or even biologic
therapies,” said Jeffrey Sosman, M.D., professor of Medicine at
Vanderbilt-Ingram. This resistance to common therapy has long
puzzled cancer investigators like Sosman, who has been working for
years to improve the use of drugs that either stimulate the immune
system (interleukin-2) or those that choke off the blood supply
(anti-angiogenic agents) to the tumor.
For 26 weeks, Kidwell drove to Nashville for weekly drug infusions.
But by February 2007, scans and a biopsy confirmed two
new potential tumors, one in each adrenal gland. The initial clinical
trial didn’t seem to be stopping his cancer.
Sosman’s colleague, Igor Puzanov, M.D., M.S.C.I., assistant
professor of Medicine, offered Kidwell a new trial of high-dose
interleukin-2 (IL-2), which stimulates the body’s immune system,
combined with a drug called bevacizumab or Avastin. Bevacizumab
is one of a new class of drugs that targets angiogenesis – the formation
of new blood vessels that tumors need to grow and thrive.
These drugs were created to interfere with the effects of mutations
like those in the von Hippel-Lindau (VHL) gene, which is implicated
in kidney cancer.
“Because VHL is mutated, the cell releases a number of factors
that promote blood vessel formation or angiogenesis,” explained
Sosman. “The cancer cell behaves like it’s starving for oxygen and
reacts that way. People realized that if you attack some of those factors
that promote blood vessel formation, you might have a very
effective therapy.”
But first, Jeff Kidwell had to get through the high-dose IL-2
therapy. Introduced for kidney cancer therapy in the early 1990s,
IL-2 is appropriate for a subset of patients who are young and
healthy, with no heart or lung disease.
“Vanderbilt-Ingram is one of the selected Centers of Excellence
for IL-2 therapy in the southeast region of the United States,” said
Puzanov. “This designation recognizes that we have special operating
procedures in place for this very intensive therapy, and we are
now No. 5 in the nation by volume of cases.”
Approximately 15 percent of patients who receive high-dose
IL-2 experience a significant shrinkage of disease that can last
“Cancer is a very long road.
It’s winding, and it’s really
bumpy...When you hit
the bump, knock the dirt off
and get back up.”
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S P O T L I G H T • K I D N E Y C A N C E R
several years. But more importantly, about 5 percent to 8 percent of
patients can be cured. Investigators still don’t know how to identify
those who will be helped.
Jeff Kidwell was willing to try, even though the treatment
required five-day stints in the hospital with several intravenous
doses of the drug every day. Then there were the side effects.
“It was the toughest drug I’ve ever tried in my life. It beat me
down so fast,” remembered Kidwell. “I had everything – nausea,
rigors, rash, peeling skin. I just quit eating and took the fluids.”
In between the hospitalizations for IL-2, Kidwell came to
Nashville for infusions of Avastin. More side effects.
“God love my care partners because they had to do the tough
part. My kids had to pick me up and put me in the recliner and take
me out of it,” said Kidwell. “My wife and my kids are my strength.”
During those months, Kidwell and his family found reason
for optimism. Scans of his adrenal glands and lung showed the
tumors were shrinking. His remaining kidney started to function
more normally.
Eventually, like many other patients, Kidwell couldn’t tolerate
additional treatments and had to stop. Surgeons removed the tumor
in his lung and confirmed it was renal cell cancer. They took out
both adrenal glands and after a rib fracture, removed a small
amount of bone from his ribs.
But in recent months, the disease appears to have stabilized. His
scans are clear. He appears to have benefitted from the explosion of
new targeted drugs that have been developed in the last decade.
“We started with just high-dose IL-2 and interferon alpha in
the early 1990s and had nothing else to offer patients for years,”
said Puzanov. “But in 2005, Nexavar was approved, then Sutent
and Avastin. Now we have half-a-dozen drugs that may slow down
the disease.”
Sosman points out that while these drugs stabilize the disease
and shrink the tumor, they don’t make it go away.
“These drugs make the disease more chronic, like diabetes, but
they don’t cure it,” explained Sosman. “These patients will relapse
and then get another drug in the family. Now I see patients who are
five or six years out from diagnosis.”
Sosman and Puzanov, with the help of patients like Kidwell,
are engaged in new clinical research trials, trying to find the answers
that will finally lead to a cure. The cancer investigators say there is a
great need for more financial support for renal cell cancer research.
These days, Jeff Kidwell can’t stop smiling when he talks
about the long stretch of time since anything new appeared on his
scans. He’s golfing again, going to UT games and spending time
with his family.
“Cancer is a very long road. It’s winding, and it’s really
bumpy,” said Kidwell. “When you hit the bump, knock the dirt off
and get back up. The good Lord has kept me around to do something.
I don’t know what it is, but if I can touch somebody who has
kidney cancer by sharing my story, my journey for the last four
years has been worthwhile.”
The Kidwell family - (left to right) son Brad and his wife Brittany, wife
Connie, Jeff, and sons Brice and Blake - enjoys a day together.
Kidney surgery
less is sometimes more
A diagnosis of kidney cancer used to require the same initial
treatment – surgical removal of the entire organ.
“Twenty years ago there was one operation and that was to
make a big, flank incision through your side, at least six to eight
inches, and remove your entire kidney,” explained S. Duke
Herrell, M.D., associate professor of Urologic Surgery at
Vanderbilt-Ingram. “That was done whether your tumor was the
size of a dime or a football.”
Over the past eight years, Herrell has been getting excellent
results with laparoscopic and now robotic surgery for removal of
kidney tumors, preserving the rest of the kidney (partial nephrectomy).
For most tumors less than 7 centimeters, removing just the
cancerous part of the kidney appears safe for cancer control and
improves the patient’s renal function, quality of life and overall
survival. Patients undergoing this “minimally invasive” surgery
also experience less pain and have a shorter recovery time.
Herrell, director of Minimally Invasive Urologic Surgery and
Robotics, has also started and developed a program using new
ablation techniques, such as radiofrequency and cryoablation, to
destroy some smaller kidney tumors. And he and his colleagues
in Biomedical Engineering are improving robotic surgery by
incorporating preoperative imaging, which shows critical internal
structures during robotic kidney surgery.
“I enjoy the challenge of being sent some of the most difficult
cases by my colleagues and of developing new innovations
and programs that produce cures while reducing pain and suffering
for our cancer patients.”
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GUT REACTION
Understanding how infection causes
stomach cancer could lead to new
treatments, prevention
B y L e i g h M a c M i l l a n | P h o t o g r a p h b y S c i e n c e P h o t o L i b r a r y
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Richard Peek, M.D., laughs at the memory of his introduction
to Helicobacter pylori – a twisted sausage-shaped
bacterium that takes up residence in the human stomach.
He was a medical student at the time – around 1987 – and
was following a patient with a bleeding ulcer. The patient had an
endoscopy procedure to view and take biopsy samples of the stomach
and intestinal tissue.
“I went to his room afterwards, and he told me that the doctor
said there were ‘helicopters’ in his stomach,” Peek recalls.
Peek didn’t know much about ‘helicopters’ then, but in the
years since, the bacterium that causes stomach ulcers and is the
major risk factor for stomach cancer has become the focus of his
research.
By studying Helicobacter pylori (H. pylori) and stomach cancer,
Peek and his colleagues hope to unlock the secrets of how infectious
agents cause cancer and find ways to prevent it.
“If we can intervene early on – to eliminate the chronic
inflammatory process caused by infection – then the chances of
reducing the cancer risk are much higher than if we treat later after
pre-malignant changes have already occurred,” says Peek, the Mina
Cobb Wallace Professor of Gastroenterology and Cancer Biology at
Vanderbilt University.
CANCER GERMS
H. pylori is an infectious agent – a bacterium – that has been
linked to an increased risk of cancer. It’s not alone. Other bacteria,
viruses and parasites are associated with a variety of cancers.
Current evidence suggests that as many as one in five cancers
worldwide may have an infectious cause.
Viruses can insert their own genes into a cell’s DNA and disrupt
the genes that regulate cell division and death. In the case of
bacteria and parasites, one of the main problems appears to be
chronic inflammation – the body makes an attempt to eliminate
the pathogen, but it fails.
“Many of these organisms have developed strategies that allow
them to persist or smolder in their hosts for decades,” Peek says.
“That’s a common theme that we’re seeing that distinguishes infectious
agents that cause cancer from those that don’t.”
It’s possible, he adds, that even more cancers will be linked to
infectious agents as technology enables the identification of previously
unrecognized bacterial and viral populations.
“Whether or not every inflammation-associated malignancy
will have an infectious cause, I can’t say, but I do think that we’re
going to be discovering more infectious agents that cause malignancy,”
Peek says.
Evolutionary biologist Paul Ewald, Ph.D., of the University of
Louisville, thinks we’ll ultimately learn that infections cause most
human cancers.
“If I were going to put my money on it, I would bet that by
2050 – hopefully earlier – we’ll have found that more than 80 percent
of all human cancer is caused by infection. The number could
be as high as 95 percent. In 1975 it was considered to be zero,”
Ewald said in an interview published last fall in Discover magazine.
If infectious agents cause cancer, then preventing infection in
the first place should provide a sure-fire way to prevent cancer.
That’s the goal of vaccines like those directed against human papilloma
virus, a major cause of cervical cancer, and hepatitis B virus,
a cause of liver cancer.
But there aren’t vaccines for every infectious agent linked to
cancer, and even if there were, they would be unlikely to reach
every person at risk. So treatments are needed to eliminate the
smoldering infections.
In the case of H. pylori, antibiotics can eliminate the infection.
The problem is figuring out who should be treated. Half of the
world’s population is infected with H. pylori, yet only about 1 percent
of infected individuals will develop stomach cancer. And the
bug may even be conferring beneficial effects to some of its hosts.
“I think there should not be widespread policies of testing and
treating individuals for many of these organisms because only a
minority of people who are infected have adverse outcomes,” Peek
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says. “For us that justifies trying to
understand how the bacteria really
causes cancer and who is most at risk.
Then we can focus treatment efforts
on those small pockets of high risk
populations.”
COLOMBIAN CLUES
Stomach cancer is the second
leading cause of cancer-related deaths
worldwide (lung cancer is first). The
highest rates of new stomach cancers
are in Japan, throughout Asia, and in
parts of South America.
One pocket of increased stomach
cancer risk sits high in the Andes
Mountains of Colombia.
As a new physician, Colombian
native Pelayo Correa, M.D., began to
compile a cancer registry in the city of
Cali, Colombia, where he was practicing.
He found that stomach cancer
dominated the list, and he noticed
that people who had come to Cali
from the Andes in the southern part
of the country had a higher incidence of stomach cancer than
those from other parts of Colombia.
“So we went there to the mountains – the first time was in
1964 – and we started doing a series of studies which are still
going on today,” says Correa, the Anne Potter Wilson
Distinguished Professor in Colon Cancer at Vanderbilt. “We have
learned many things with that population.”
In the early years, Correa and his colleagues examined biopsy
samples and characterized the progression of gastric lesions – a cascade-like
process that begins with inflammation of the stomach’s
mucosal lining (gastritis) and proceeds stepwise to cancer. They
estimated the rate of transition for lesions, and they sought factors
that were contributing to the region’s high cancer rate.
They didn’t consider H. pylori – because it hadn’t yet been
identified. The bug and its link to gastric ulcers were discovered in
the 1980s, and in 1994 the International Agency for Research on
J O E H O W E LL
“Whether or not every
inflammation-associated
malignancy will have an
infectious cause, I can’t
say, but I do think that
we’re going to be
discovering more
infectious agents that
cause malignancy.”
Richard Peek, M.D.
“There’s no question that
what drives the carcinogenic
process is the infection of this
bug,” Correa says. “But it’s
modulated. Very few people
will get cancer.”
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Stomach cancer incidence
H pylori prevalence
21-70 per 100,000 population in males
75% and above
65-74%
55-64%
Below 55%
Pelayo Correa, M.D.,
thinks a “perfect storm”
of genetic and
environmental factors is
responsible for the high
risk of stomach cancer
in the mountains of
Colombia. “…It’s the
bug and the genetics of
the person and the diet
all together.
J O E H O W E LL
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Maps of stomach cancer incidence and H. pylori infection rates
show areas of overlap in Asia and South America. Interestingly, H.
pylori infection rates are high in Africa, but stomach cancer incidence
is low.
By tracking ancestry of human populations and of H. pylori
strains, investigators may be able to understand how the interactions
between germ and host cause disease.
Sources:
GLOBOCAN 2002, (World Health Organization)
Parkin DM (Int J Cancer 2006; 118: 3030-3044)
Cancer classified H. pylori as a group 1 carcinogen – an agent that
is carcinogenic to humans.
“There’s no question that what drives the carcinogenic process
is the infection of this bug,” Correa says. “But it’s modulated. Very
few people will get cancer.”
But who will get cancer? And can these people be identified
and treated to prevent the cancer from developing?
Correa knew that people in the coastal regions of Colombia
had very low rates of stomach cancer, and he saw a golden opportunity
to compare the two populations in order to understand
what puts the mountain people at high risk.
The investigators quickly learned that H. pylori infection
alone wasn’t the culprit.
“The risk of cancer in the mountains is 25 times higher than
at the coast, but the infection with the bug is the same – about 80
percent of people are infected,” Correa says. “It’s much more complicated
than infection alone.”
The two populations have provided a rich resource for Correa
and his collaborators. Over the years, the investigators have discovered
that differences in the types of H. pylori (“strains”) that infect
the two groups, how a person’s immune system responds to the
infection, and environmental factors like diet and co-infection
with parasites all contribute to the varied risk for stomach cancer.
“It looks like it’s multi-factorial – it’s the bug and the genetics
of the person and the diet all together,” Correa says. “And in the
mountains you have the perfect storm – the worst bugs, the most
susceptible hosts, and a diet high in salt and low in fruits and vegetables.
It all coincides.”
BAD, BAD BUGS
Among the “worst bugs” are strains of H. pylori that express
certain bacterial virulence factors, including a group of linked
genes called the “cag pathogenicity island.” Infection with strains
Down the hatch
How an Australian doctor showed that
bacteria cause stomach troubles
In the early 1980s, physicians thought they knew what
caused ulcers – it was stress.
“If you had an ulcer, you had it for life. It meant that
you had to be on acid suppression, you had to not smoke,
you had to eat a bland diet…and it was thought that in
times of stress, your ulcers might flare,” recalls Keith
Wilson, M.D., professor of Medicine and Cancer Biology at
Vanderbilt University.
Barry Marshall, M.B., B.S., a clinical fellow at the time,
and pathologist Robin Warren, M.B., B.S., in Perth,
Australia, had another idea. They believed that bacteria
were causing inflammation (gastritis) and ulcers.
Over the course of several years, Warren had noticed
small curved bacteria colonizing the lower part of the
stomach in about half of all biopsies he examined. And he
saw signs of inflammation, always close to the bacteria.
In fact, other pathologists had reported the presence
of curvy bacteria in the stomach – since the late 1800s –
but the observations were ignored. Scientific dogma held
that bacteria couldn’t colonize the stomach with its harsh
acidity and pumping action, so the bacteria in biopsy samples
were believed to be contaminants.
Marshall succeeded in growing the bacteria from tissue
samples in culture, but he was unable to infect any
animal models to show that the bacteria caused gastritis.
Facing skepticism from the medical establishment, he
opted to infect a human: himself.
He had an endoscopy procedure to show that he was
not infected; then he mixed up a flask full of bacteria and
guzzled it.
The rest, as they say, is history. Marshall developed
severe gastritis, a precursor to ulcer disease. Although his
infection appeared to spontaneously clear, Marshall treated
himself with antibiotics to be sure of the bug’s elimination
from his stomach.
He and other investigators were then able to demonstrate
in patients that antibiotic therapy eliminated gastric
ulcers.
For their discovery of Helicobacter pylori and its role in
gastritis and peptic ulcer disease, Marshall and Warren
received the 2005 Nobel Prize in Physiology or Medicine.
“It really blew the conventional thinking out of the
water to say this one bacteria is the cause of ulcers – and
oh, by the way, it’s also a cause of gastric cancer,” Wilson
says. “The discovery of H. pylori was huge in terms of people
not dying from ulcer disease – if you detect it and treat
it, they should never have an ulcer again.”
– by Leigh MacMillan
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bacteria
viruses
parasitic worms
Cancer contagions
Infectious agents may cause chronic inflammation, suppress the immune
system, or directly affect a cell’s DNA. Any of these pathways may increase
a person’s risk for cancer.
INFECTIOUS AGENT
Helicobacter pylori
Campylobacter jejuni
Chlamydia trachomatis
Chlamydia psittaci
(parrot fever)
Chlamydia pneumoniae
Borrelia burgdorferi (Lyme disease)
Human papilloma viruses (HPVs)
Hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Epstein-Barr virus (EBV)
Human immunodeficiency virus (HIV)
Human herpes virus 8 (HHV-8)
Human T-lymphotrophic virus-1 (HTLV-1)
Opisthorchis viverrini,
Clonorchis sinensisare
Schistosoma haematobium
[Source: American Cancer Society]
ASSOCIATED CANCER
stomach cancer,
stomach MALTomas
(mucosa-associated
lymphoid tissue
lymphomas)
digestive tract MALTomas
cervical cancer
ocular adnexal (eye)
MALToma
lung cancer
skin MALToma
cervical cancer, head and
neck cancers
liver cancer
liver cancer
nasopharyngeal cancer,
Burkitt lymphoma, Hodgkin
disease
Kaposi sarcoma, cervical
cancer, lymphomas
Kaposi sarcoma, lymphomas
adult T-cell
leukemia/lymphoma
cancer of the bile ducts
bladder cancer
of H. pylori that include cag genes (cag-positive strains) increases a
person’s risk for severe gastritis and stomach cancer.
Peek and his colleagues are continuing to search for H. pylori
factors that play a role in carcinogenesis. They are using proteomic
technologies to identify the proteins expressed by different H.
pylori strains – from Colombian patients with and without cancer.
They’ve also demonstrated that virulence factors interact with
environmental factors, like a high-salt diet.
“Dr. Correa’s group has known for years that populations with a
high-salt diet (such as the Andes population) have a higher risk for
gastric cancer,” Peek says. “It could be that salt itself damages the
stomach, or it might be working in synergy with H. pylori infection.”
To explore a possible interaction between salt and H. pylori,
Timothy Cover, M.D., professor of Medicine at Vanderbilt, Peek
and colleagues studied gene expression in cag-positive H. pylori
strains exposed to high-salt conditions. They found that high salt –
at levels achievable in the human stomach – increased the expression
of certain virulence factors.
Keith Wilson, M.D., professor of Medicine and Cancer
Biology at Vanderbilt, and his team have demonstrated that H.
pylori bugs alone – without contributions from the human host –
have the ability to cause cancer. They have infected gerbils with H.
pylori strains from the high- and low-risk regions of Colombia, and
they’ve shown that the high-risk strains cause more dysplasia (one
stage in the cancer cascade) and cancer compared to the low-risk
strains.
They’ve also discovered a mechanism that could explain the
difference.
They previously showed that H. pylori induces expression of a
protein called spermine oxidase, an enzyme whose action produces
hydrogen peroxide. Hydrogen peroxide generates free radicals (oxidative
stress), which can damage cellular components, including DNA.
Wilson and his colleagues found that high-risk H. pylori
strains induced higher levels of spermine oxidase in cultured gastric
cells and in gerbils, compared to low-risk strains.
“We think that this spermine oxidase pathway within the
epithelium, in response to H. pylori, is a major source of the oxidative
stress that can initiate carcinogenesis in the stomach,” Wilson
says. “It’s very exciting as a proof-of-principle that we can take the
high-risk strains of H. pylori out of people, and that they cause
more oxidative stress and DNA damage in cells, and more cancer
in gerbils.”
Not every person colonized by high-risk or virulent strains of
H. pylori gets cancer though, which suggests that other factors –
such as a person’s inflammatory response to the infection – contribute
to cancer risk.
Individuals who have genetic variations that cause them to
produce high levels of certain pro-inflammatory molecules (IL-
1beta and TNF-alpha) have a higher risk of developing gastric cancer,
but only if they are infected with H. pylori, Peek explains. And
if they are infected with more virulent strains, their risk of gastric
cancer is increased 90-fold.
“It looks like there is a distinct interaction that’s occurring
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between the bacteria and the host
genotypic profile that augments the
risk of gastric cancer,” he says.
J O E H O W E LL
“It really emphasizes
why we need to learn
about how H. pylori
causes gastric cancer
and what puts people at
risk, because there are
plenty of reasons not to
just treat everyone
who’s infected.”
Keith Wilson, M.D.
A COMPLICATED RELATIONSHIP
H. pylori’s persistence in colonizing
the human stomach, and the fact
that only a small percentage of the
people infected have ill effects, raises
the question: is this bug doing something
beneficial?
There’s intriguing evidence that
infection with H. pylori may protect
the esophagus – perhaps by reducing
acid secretion – and may prevent the
development of allergic and autoimmune
diseases – perhaps by promoting
certain types of immune responses.
Retrospective studies have pointed
to this inverse relationship –
esophageal reflux disease (Barrett’s
esophagus), esophageal cancer, asthma
and other allergic disorders occur
more frequently in people who are not
infected with H. pylori.
The former director of
Vanderbilt’s Division of Infectious Diseases, Martin Blaser, M.D.,
now at New York University, advocates caution in our medical
approaches to H. pylori, Correa says.
“He says that curing this infection is an unnatural thing –
that we came out of Africa together 60,000 years ago, and we’re
still together,” Correa says.
As H. pylori infection rates have fallen in countries like the
United States, possibly because of increased use of antibiotics during
childhood, the rates of esophageal reflux diseases, asthma and
other allergic disorders have risen, Peek points out.
“It’s very intriguing to think that long term colonization with
H. pylori may prevent diseases that we see escalating at alarming
rates in the developed world,” he says.
We appear to have a complicated relationship with these
“companions” of ours.
“It really emphasizes why we need to learn about how H.
pylori causes gastric cancer and what puts people at risk, because
there are plenty of reasons not to just treat everyone who’s infected,”
Wilson says.
The investigators expect that their studies of H. pylori will
identify concepts and mechanisms that apply broadly to inflammation-induced
cancers elsewhere in the body.
“Inflammatory bowel disease has a very high risk of colon
cancer – so understanding how inflammation in the colon may
initiate the carcinogenic cascade is important because the incidence
of those diseases is going up,” Peek says. “I think what we understand
about a very defined etiologic agent – H. pylori – and a very
defined disease – gastric cancer – can be broadened to other diseases
that are more common and incur more of a burden on the
U.S. population.”
It’s been an interesting journey since he first learned about
‘helicopters’ in his medical school days, Peek says. And he’s looking
forward to the discoveries to come.
Rotor up, and away.
H. pylori’s persistence in colonizing
the human stomach,
and the fact that only a small
percentage of the people
infected have ill effects, raises
the question: is this bug
doing something beneficial?
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innovation
SOWING THE SEEDS OF
How the American Recovery & Reinvestment
Act is stimulating cancer research
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In
an economic crisis that has led to
some of the highest unemployment
rates since the Great Depression,
Sergey Ivanov, Ph.D., is very relieved
to have found a position at
Vanderbilt-Ingram Cancer Center.
Ivanov’s wife had accepted a new
position at Vanderbilt, so the couple
moved from New York to Nashville in
2009. But Ivanov didn’t have a job
prospect lined up. He was out of
work for several months – and was
growing a bit concerned.
But the influx of research grants
from the 2009 American Recovery
and Reinvestment Act – the “stimulus”
bill passed by Congress in
February 2009 – had opened up an
opportunity that fit with Ivanov’s
years of expertise in developing mouse
models of disease at the National
Cancer Institute and translational
research tools in New York University.
He was hired in November 2009
as a research assistant professor in the
lab of Wendell Yarbrough, M.D., who
was the recipient of two “stimulus”
grants from the National Institutes of
Health. The two-year Challenge
Grants (a highly competitive grant
category with about 4 percent of
applications funded) provided more
than $1.4 million for Yarbrough’s lab
to further his research in head and
neck cancer and to develop a new
mouse model for salivary gland cancer
– a rare but vicious type of cancer
that can affect the facial nerves.
Little is known about what causes
salivary gland cancer or how best to
treat it.
“There is no way to treat salivary
carcinomas, except for surgery,”
Ivanov explains. “And (surgery) is not
ideal at times because sometimes
nerves get involved. To avoid this surgical
intrusion, it would be better to
have a different method of treatment.”
Ivanov immediately went to work
on developing a new mouse model for
salivary gland cancers. Developing a
so-called “xenograft” model, Ivanov
takes human tumor cells that have
been removed during biopsies or surgery,
grows them in culture, and
transplants them into mice so that the
mice grow “human” tumors.
If successful, the mouse model
will help researchers determine the
molecular pathways that drive this
cancer and screen chemotherapy
drugs against the disease, Ivanov says.
Seed money
Ivanov’s new position – and the
research project he was hired to work
on – are examples of how the federal
“stimulus” funding is enriching the
research environment at Vanderbilt-
Ingram.
The American Recovery and
Reinvestment Act has provided some
$21 billion for scientific research and
development, the purchase of scientific
equipment, and science-related
construction, according to the Web
site www.scienceworksforus.org.
Researchers at Vanderbilt
University Medical Center have
secured more than $73 million from
155 research grants. The funding is
estimated to support 105 FTEs (fulltime
equivalents, or positions), according
to Vanderbilt University’s office of
Contract & Grant Accounting.
Of this total, 75 NIH grants
were awarded to Vanderbilt-Ingram
Cancer Center members, providing
more than $40 million to support
new and ongoing cancer-related initiatives.
The funding is supporting
projects that range from the most
basic molecular mechanisms of cancer
to population-based research to evaluate
cancer disparities and risk factors.
Researchers at
Vanderbilt
University
Medical Center
have secured
more than $73
million from 155
research grants.
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AN N E R AY N E R
In his remarks at the National Institutes of Health in
September 2009, President Obama discussed the progress that has
been made in cancer research – and the opportunities that the
stimulus funding will provide:
“In cancer, we’re beginning to see treatments based on our
knowledge of genetic changes that cause the disease and the genetic
predispositions that many of us carry that make us more susceptible
to the disease. But we’ve only scratched the surface of these
kinds of treatments, because we’ve only begun to understand the
relationship between our environment and genetics in causing and
promoting cancer.”
While there has been much debate about whether research
grants actually stimulate the economy in the short-term, the more
important impact of this research funding may be to plant the seeds
of innovation that fuel scientific progress. NIH director Francis
Collins, M.D., Ph.D., said in his introduction of the President:
“I’ve reviewed hundreds of these grant summaries myself. And
they propose some of the most innovative and creative directions
for research that I have ever seen. …We’re investigating new problems
with powerful new tools and looking at old problems from
entirely new perspectives.”
Stimulus funding awarded to Wendell Yarbrough, M.D. (right), provided
Sergey Ivanov, Ph.D., (left) a research position and the opportunity to develop
a mouse model of salivary gland cancer.
The stimulus has contributed to job creation and retention at
Vanderbilt-Ingram: Yarbrough’s funding has allowed him to retain
one position and to hire one new faculty-level position (Ivanov),
and he hopes to add another postdoctoral or junior faculty-level
researcher soon. But he feels that the bigger impact is in cultivating
research areas that have traditionally been considered too highrisk
to fund.
“I think that the short-term gain and the biggest long-term
impact will relate to stimulating and advancing projects that are
higher risk, but also higher potential gain,” says Yarbrough, an
Ingram Professor of Cancer Research and director of the Barry
Baker Laboratory for Head and Neck Oncology.
“These projects will, in aggregate, stimulate and advance areas
of research that were previously more stagnant.”
Yarbrough’s second stimulus grant supports modeling human
head and neck cancers in mice to look for responses to targeted
therapies. An effective mouse model would allow for faster testing
of potential new drugs for these cancer types and, eventually, to
better match patients with specific drugs based on genetic markers
within the patients’ tumors.
This funding, Yarbrough says, has allowed his lab to “accelerate
our research designed to advance personalized therapy for cancer.”
Digging deeper
The funding boost not only allows H. Charles Manning,
Ph.D., to accelerate the pace of his existing work, but also to “dig
a little deeper into each project.”
Manning, an assistant professor of Radiology and Radiological
Sciences, received two stimulus grants (including one Challenge
Grant) totaling more than $1.6 million to develop and validate
biomarkers that could aid in detecting cancer with non-invasive
imaging methods.
“Overall, I think we are able to conduct potentially higherimpact
studies,” Manning says. Since these types of imaging studies
are costly, the stimulus has allowed Manning to expand the
number of imaging studies conducted overall and “grow our repertoire
of assays for validation, directly impacting the nature and
complexity of questions we can ask in our research.”
Manning’s Challenge Grant supports investigation of a tracer
called 18 F-fluorothymidine (FLT) in positron emission tomography
(PET) scans. FLT is taken up by rapidly dividing cells. Because
tumors are composed of rapidly dividing cells, they take up FLT
and show up as bright spots on PET scans. Manning is investigating
what types of cancers can be evaluated with FLT in mouse
models of colorectal cancer and in human patients.
Biomarkers like FLT are important for diagnosis and for monitoring
response to cancer therapies, which is a critical component
of personalized medicine.
“Molecular imaging biomarkers, like FLT, may enable us to
determine whether a drug is working as early as a few hours after
administration as well as predict whether patients will continue to
respond over time,” Manning says. “This information could spare
patients the expense and potential side effects of ineffective therapies.”
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Sustainable science?
The stimulus funding has also provided a major boost to
research on lung cancer – the leading cause of cancer deaths
worldwide.
David Carbone, M.D., Ph.D., received two grants totaling
$1.7 million to advance his lung cancer research. The funding
from the first grant (also a Challenge Grant) will be used to evaluate
inherited and acquired genetic characteristics of lung cancer in
African-Americans.
African-Americans have a significantly greater risk of developing
lung cancer – and of dying from the disease – than other ethnic
groups.
Carbone and collaborators at Meharry Medical College will
search for genetic mutations that may explain the higher rates of disease,
as well as differences in how some patients respond to treatment.
This project “is a totally new and nationally important study
as (African-Americans) have been dramatically under-studied to
date – and takes advantage of our unique partnership with
Meharry,” says Carbone, a professor of Medicine, Cell and
Developmental Biology, and Cancer Biology.
The second grant – a $700,000 supplement to an existing
grant – will be used by Carbone and co-investigator Pierre
Massion, M.D., to test 100 proteins in the blood for their possible
utility in detecting and/or diagnosing lung cancer.
Such biomarkers may allow the development of a simple
blood test for diagnosing lung cancer – or identifying patients at
high risk of developing the disease.
While these grants have allowed Carbone to hire new staff
and have enabled work that he says would not have been possible
otherwise, he is concerned about the long term.
The stimulus grants have a “tremendously positive short-term
impact, both on the science and on employment in the biomedical
research sector,” Carbone says. “But I am concerned about sustainability
of the funded initiatives and that there may be a ‘crash’ at
the end of funding.”
Sustainability has been one of the major questions about stimulus-funded
research. Most stimulus-funded grants have a two-year
term, and many wonder what happens after the two years are up.
“There are many new, outstanding projects now funded
nationwide, even if just for just two years, that will likely evolve
into important programs and be self-sustaining through a variety
of mechanisms,” says Manning. “However, we need to be thinking
about sustainability for the long-term and how we can keep stimulus-funded
research going.”
Jennifer Pietenpol, Ph.D., director of Vanderbilt-Ingram, is
also worried about a potential stimulus funding “bubble.”
“We in the research community are thrilled about the influx of
stimulus funding, but we are also concerned about an artificial
‘bubble’ that then ‘pops’ when the stimulus funding ends,” she said.
“This speaks to the stability of federal funding for medical
research overall, but also the importance of private philanthropy to
help take the most promising projects from the stimulus funding
and move them forward.”
“Grand Opportunity” for
breast cancer drug development
A two-year, $4.7 million “Grand
Opportunities” stimulus grant
from the National Institutes of
Health is funding a cancer drug
discovery program for “triplenegative”
breast cancer, a particularly
deadly form of the disease
that accounts for 25 percent of all
breast cancer deaths and disproportionately
affects African-
American women.
Triple-negative breast cancers
do not express receptors for the
hormones estrogen and progesterone
and the human epidermal
growth factor receptor 2
(HER2) – three common targets
of breast cancer therapies. This
makes triple-negative tumors
difficult to treat.
Researchers will try to identify
genes that drive the different
subtypes of triple-negative
breast cancer and then fashion
drugs to block the action of the
proteins encoded by the genes,
with the intent of killing the cancer
cells.
Lawrence Marnett, Ph.D.,
director of the Vanderbilt
Institute of Chemical Biology
(VICB) and the grant’s principal
investigator, predicted that by
the end of the two years of the
grant, “we will have built a platform
to identify the best potential
targets for triple-negative
breast cancer.”
“This is really personalized
drug discovery,” said Marnett,
University Professor, Mary
Geddes Stahlman Professor of
Cancer Research, and director of
the A.B. Hancock Jr. Memorial
Laboratory for Cancer Research.
“We think (it) represents the
model for the future.”
The grant supports the work
of the Vanderbilt Molecular
Target Discovery and
Development Center – a joint
effort of the VICB and the
Vanderbilt-Ingram Cancer
Center. Investigators leading the
various projects of the initiative
are: Jennifer Pietenpol, Ph.D.,
director of the VICC; Carlos
Arteaga, M.D., director of VICC’s
breast cancer program; David
Cortez, Ph.D., co-director of the
VICC Genome Maintenance
Program; Stephen Fesik, Ph.D.,
the Orrin H. Ingram II Professor
of Cancer Research; and David
Weaver, Ph.D., director of the
VICB high-throughput screening
facility.
– by Bill Snyder
For now, Ivanov isn’t letting that two-year window worry him;
he has a job to do.
Even though he started on his project just a few months ago,
he is making rapid progress and thinks he should be able to
accomplish the goal of developing the first mouse model of salivary
cancer by the end of the two-year period.
“The goals of the grant seem very achievable,” he says. “In this
particular case, this is a new model for salivary tumors that has
never been created before. And when you consider the lack of
information about how salivary tumors grow, the drivers of the
disease, and the mutations or pathways involved, this could really
be a breakthrough.”
-Dagny Stuart contributed to this story
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CANCER 2.0 > >>
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Harnessing computing
power for cancer
research and care
>
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n iTunes U, a
lecturer predicts that we
will one day be routinely
giving drugs to computers.
When you get sick, someone will load your medical history and
your genome sequence (and perhaps other selected data about your
biochemical composition) into a simulator. As various drugs are
entered, you’ll learn of their predicted effects in your body.
While such scenarios may lie in our (perhaps still distant) future,
it will take time – and some major computing power – to get there.
Biology has quite recently entered a golden age. Majestic,
beckoning mountains of biological data – composed primarily of
information about our genomes and the subtle differences among
them – are filling up the planet’s servers at explosive rates.
Computer-assisted analysis of such huge data sets is the realm of
“bioinformatics” – a discipline that applies information/computer
science approaches to help researchers make sense of this biological
information.
But that is only part of the equation; to achieve this futuristic
scenario will also require the contribution of “biomedical informatics,”
a field focused on applying the power of computers to
health care, through, for example, electronic medical records and
decision support systems.
Though they had divergent beginnings, the fields of bioinformatics
and biomedical informatics are now beginning to merge.
“We’ve had bioinformatics, which essentially grew out of
molecular biology and had the vocabulary and the cultural values
of wet-bench biologists. It was just tying to figure out how life
works, what’s the machinery like,” says Dan Masys, M.D., professor
and chair of Biomedical Informatics at Vanderbilt, one of the
nation’s largest biomedical informatics departments.
“And then we had clinical informatics, which grew historically
out of people building electronic medical record systems for hospitals.
“These two types of people, if you put them in a room they
would not have much to talk about, but what we’re seeing is the
emergence of this relentless convergence of these tools in an area
we call clinical bioinformatics. And that’s about understanding
molecular patterns that have direct relevance to human health and
disease and health care decision-making.”
Life encoded…and corrupted
It all starts with DNA, an information storage molecule in the
nucleus of cells. Like a computer stores information in a digital
code of zeros and ones, DNA encodes the basic instructions for life
using four chemical “letters” or bases: A, T, C and G (adenine,
thymine, cytosine and guanine). These letters, positioned in
“nucleotide” pairs, form the rungs of DNA’s “twisted ladder” or
double helix. The double helix unzips down the center, allowing
the sequence on either side to be transcribed as RNA molecules. In
tiny automated workshops called ribosomes, some of the RNA gets
read off and translated into big, bad proteins, the manifold
machinery of cellular life.
Genes are a knotty concept, but they’re basically sections of
DNA corresponding to proteins, or to otherwise interesting bits of
RNA. They function in networks, with some genes making products
that activate and deactivate other genes. There are approximately
22,000 genes in the human genome.
As our cells divide and the genetic code is replicated and
bequeathed to daughter cells, despite a lot of error checking, the
nucleotides are vulnerable to sporadic scrambling – a “corrupted
code,” in computer-speak. Radiation, chemical exposures and viruses
can also cause scrambling. When you add it all up, we’re riddled
with random mutations: single-nucleotide changes, insertions, deletions
large and small, chromosome inversions, translocations
between disparate chromosomes, and amplification – gene duplication
that can potentially boost production of a given gene product.
In the time it takes to read this article, you’ll develop umpteen
thousands of new mutations, but an overwhelming majority of
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Dan Masys, M.D., leads one of the
nation’s largest biomedical informatics
departments in its quest to
improve research and clinical care
through the powers of computing.
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S U SAN U R M Y
mutations come to naught, and only on very rare occasions are
some mutations plucked from obscurity and thrust into consequential
roles. Germ-line mutations (those in reproductive cells)
can be a ticket out of the primordial sludge (the only ticket).
Cancer can arise when somatic mutations — those in bone, brain,
blood, skin or what have you — randomly mount up into some
unlucky combination, giving some cell the keys to unchecked
growth. Odds worsen as we age and begin carrying around more
and more mutations.
Pattern finders
With so many ways for so many nucleotides to fall out of
proper sequence, one begins to grasp the role of computers in
understanding genetics and cancer.
Take genome sequencing, which is generally preceded by
chopping up an organism’s DNA into thousands of varying
lengths, amplifying the fragments (so that you’ve got more material
to work with) and locating the letters along the fragments (with an
old method called electrophoresis, which reveals the positions of
nucleotides by virtue of their relative weights). Once these myriad
ordered sets are loaded into a computer, an algorithm (a set of
rules for solving a problem) can then be put to work, attempting
to sequence as much of the code as possible based on overlap
found among the sets.
Without computers, it’s hopeless. But bioinformatics has
never been primarily about technology for Masys, who, years ago
as a young oncologist, recognized the power of computers in revolutionizing
biology and medicine.
It’s instead about “understanding the semantics of the data. It’s
about finding related observations about biologic behaviors of cells
in a variety of different kinds of databases – genes, proteins, carbohydrates,
control factors,” he says.
“At a molecular level, it’s figuring out how the hip bone is
connected to the thigh bone.”
The power of computers in finding biologically important
patterns is illustrated by a pivotal event from the mid-1980s.
Researchers at computers in London and San Diego were struck to
find that an entity called the v-sis oncogene, which they regarded
as a cancer gene, was the spitting image of a harmless – in fact,
essential – gene that molecular biologists had identified as producing
a growth factor.
“A light went on,” says Masys. “The oncogene was just the
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growth factor gene switched on at the wrong time, when cells
shouldn’t be proliferating.”
“That was a key insight in the history of informatics, because
that pattern-matching done by computers was just a matter of
searching through databases of gene and protein sequences that
had been deposited by many different labs for many different purposes,
and it led to a key biological insight that nobody in the
world expected.”
Where illness is concerned, the focus narrows to a particular
disease, with analysis of sample after sample in a search for molecular
patterns – comparisons between disease samples and normal
samples, samples from patients sensitive to a particular drug and
patients not sensitive, samples from patients who had a recurrence
and patients who remained disease free. (A favored strategy for
narrowing in on disease-related genes and their associated intracellular
signaling pathways is microarray analysis, an economical
method revealing variable gene expression across part or all of the
genome.) Ultimately, the hunt is for biomarkers — traceable substances
that reliably indicate biological states.
But a data pattern and a cause-and-effect relationship are
quite different things.
Associate Professor Zhongming Zhao, Ph.D., M.S., is a pattern
finder.
“It’s always association, whether this gene or set of genes is
potentially related to this disease,” he says. “If you find a pattern in a
gene or a set of genes that’s always different by chance between two
sets of samples, it’s a potential biomarker. Then you try to validate.”
Zhao came to Vanderbilt-Ingram in late 2009 as chief bioinformatics
officer and director of the Bioinformatics Resource
Center. In 2000, as he saw the human genome project reaching
completion, Zhao decided to go back to school for a master’s
degree in computer science – this after already having earned master’s
degrees in genetics and biomathematics and a doctorate in
human population genetics.
“I realized the coming of a lot of genomics data. I decided to
study computer science because I knew we couldn’t do it by hand;
we needed to analyze by some intelligent modeling algorithm.”
For diseases like cancer, molecular biomarkers – for a given
diagnosis, prognosis, drug response – usually come with probabilities
attached. Gene expression profiling might tell you, for example,
S U SAN U R M Y
Zhongming Zhao, Ph.D., M.S., uses
bioinformatics approaches to study
complex diseases like cancer, aiming
to uncover genetic drivers of cancer and
genes that may be involved in an individual’s
response to certain therapies.
> >>
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that it’s 80 percent likely that you have prostate cancer. According
to Zhao, more sophisticated integration of data is destined to yield
increasingly probative, multi-dimensional biomarkers.
“We encourage cancer investigators right now to always analyze
genomic data from two platforms. We want to try to perform
more advanced analysis, combining DNA sequences, mRNAs, proteins
and their interactions.”
Connecting genes to
clinical practice
There’s a project taking shape at Vanderbilt-Ingram that
hinges on the power of bioinformatics and biomedical informatics.
Vanderbilt is preparing to launch routine genotyping of tumor tissues,
looking for known and suspected genetic biomarkers that
could help steer more precise, less toxic cancer treatment.
Chemotherapy is toxic and hit or miss. The emergence of
molecular biomarkers is leading to finer and finer sub-typing of
cancer and a rush to discover targeted drugs designed to interfere
with abnormal molecules while remaining nontoxic to normal cells.
Targeted cancer drugs are entering the pipeline and a few have
already emerged with accompanying genetic biomarkers for predicting
patient response.
Associate Professor William Pao, M.D., Ph.D., is an oncologist
and cancer biologist with a special interest in tyrosine kinases
(TKs), a group of intracellular signaling enzymes, which, when
mutated so as to become stuck in the “on” position, are implicated
in cancer. He has studied the mechanisms of targeted drug compounds
that inhibit certain mutant TKs while allowing normal
TKs to carry on.
As director for personalized medicine at Vanderbilt-Ingram,
Pao has led the planning for routine genotyping of tumor tissues.
Massachusetts General Hospital and Sloan-Kettering are two centers
known to have already begun routine clinical genotyping of
cancer tumors. At Vanderbilt there will be a major new twist: concurrent
with these new clinical assays, and building on the Medical
Center’s strengths in clinical informatics (e.g., electronic medical
records), Vanderbilt-Ingram will begin developing a system for personalized
medicine.
As more and more tumor genotyping is digitally collated with
other information from medical records, the expectation is that a
Clinical bioinformatics is “about understanding
molecular patterns that have
direct relevance to human health and
disease and health care decision-making.”
new understanding of cancer and a new level of clinical decision
support will emerge. This is clinical informatics, the bailiwick of
Mia Levy, M.D., who arrived last August as clinical informatics
officer at Vanderbilt-Ingram.
Levy recalls entering medical school (after undergraduate
study in bio-engineering and work as a programmer) thinking that
“I might not even practice medicine and I would just go into
informatics.
“I wanted to know what the real problems of physicians were;
I didn’t want to just build tools without really understanding what
their issues were.”
In her third year, during a rotation at the National Library of
Medicine, she foresaw an increasing role for informatics in the
understanding and treatment of cancer, and she wound up combining
training in oncology with work toward a doctorate in biomedical
informatics.
“I know [Cancer Center Director] Jennifer Pietenpol likes to
brag that there’s less than a handful of medical oncologists who are
also trained in informatics and we have two of them at Vanderbilt –
Dan Masys and myself – so that’s pretty cool.”
Before Levy the student espied the rich informatics vein in
oncology, there was a more strictly personal side to her interest in
this medical specialty. During her first year in medical school, her
mother was diagnosed with metastatic breast cancer.
“She was fortunate to live for seven years before she passed
away, a few years ago. And I became a breast oncologist,” Levy
says. “I’m Jewish, and so many women in my mother’s sphere have
been affected by breast cancer. So maybe it’s a little self preservation,
but it’s also that I’m just trying to help any way I can.”
Research by Pao and others has established that a single point
variant (single DNA letter change) can all by itself signal a likely
>>
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protein malfunction and thus furnish a response prediction for a
targeted drug. Conversely, the lack of a point variant at some given
site may forecast zero response to some given drug.
At Vanderbilt, whenever pathology is positive for certain types
of cancer (starting with lung cancers and melanomas), genotyping
in the clinical molecular biology lab will be initiated automatically,
screening cancers for approximately 40 different mutations in up to
nine different genes. The mutation sites qualify as biomarkers for
predicting response to established drugs or drugs in clinical trials.
“It’s at the gene level that we’re going to be providing decision
support to our clinicians: is EGFR mutated or not, is KRAS
mutated or not, is BRAF mutated or not,” Levy says.
She has been pleased to learn that the lab apparatus for these
assays will be returning structured, machine-readable data, but that
still leaves questions about how best to present the results to clinical
teams.
“This is not like a chemistry panel done for a hundred years.
This is new genetic data, which has not been well represented in
the electronic health record before. There’s a whole nomenclature
for genes and amino acids. Our system will need to pull in these
results and represent them in the medical record in a coded way
that people can reason with.”
She says the decision support initially will amount to the display
of any clinically relevant genotype results, followed soon by
flags and automated messages when a result suggests that enrollment
in a given clinical trial should be considered.
AI in the hospital
Levy is also charged with a much larger project: bringing biomedical
informatics to aid treatment prioritization for cancer
patients. She stressed that this new automated reporting of genotyping
is only a starting point. Both she and Masys envision a system
that, practically on its own, will be able to generate knowledge
about the best ways to treat cancer – a sort of “artificial intelligence”
for health care.
“We think ... that within three to five years
you could get your entire genome in your
electronic medical record for less than the
price of a CT scan, for about $1,000.”
“What we’re going to do with the next generation of decision
support is record decisions, then track patients and see what happens,”
Masys says. “If we can harvest molecular patterns and how
their stories play out clinically, in a short time we can improve the
treatment rules, instead of waiting years for clinical trial results. It’s
this very interesting synthesis of practice and research, being fused
together and building at a fast pace.”
This concept is often given as “today’s patients informing
tomorrow’s care,” Levy says. “The premise is that we don’t know
what patterns will emerge, what will turn up as relevant, so we
need a system that can learn that and form a basis for decision
support.”
Standardized cancer patient assessment is a major prerequisite
for the learning system envisioned by Levy and Masys. The system
will use all manner of standardized data – lab results, diagnoses,
co-morbid conditions, disease staging, treatment selections, details
on the management of treatment, and finally patient response.
“If we have all that, we can begin to do population-based
analysis, and we can test and tweak treatment selection methods
until we reach optimum outcomes,” says Levy. “But getting people
to put in structured data is always a time-suck and they’re always
looking for someone else to do it.”
So the challenge is getting more patient information into standardized
and machine-readable form without slowing down work
in patient care areas and clinical labs.
Take imaging results for cancer. To have any hope of studying
patterns of tumor response across a population, the radiology
reports for each patient need to be consistent across the course of
treatment, at every stage measuring the same tumors, arriving at a
longitudinal string of values representing the patient’s tumor burden.
And because this makes for relatively laborious reporting, it’s
currently done only for clinical trials; according to Levy, most
oncologists who work with adult patients have grown inured to
receiving radiology reports that don’t clearly connect up from one
stage of treatment to the next. What’s more, radiology reports currently
come back as unstructured text.
Levy has a plan for pulling consistent, structured radiology
findings into a cancer patient assessment system. An ad hoc community
of computer experts has collaborated over the Web to create
an open-source markup tool for radiology images. With images
loaded, users demarcate tumors with mouse clicks and the tool
spits out the tumor dimensions. Levy is planning to import this
tool into the Vanderbilt system, setting it up so that, as radiologists
call up new images for cancer patients, the system will automatically
retrieve any past reports and supply guidance for generating
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Clinical Informatics Officer, Mia Levy,
M.D., is one of only a handful of
medical oncologists also trained in
informatics. She is tasked with bringing
biomedical informatics to aid in
clinical decision-making.
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standardized, structured follow-up data, the sort that will be allowable
in the cancer population assessment database.
Cancer pathology (based on visual examination of cells) is
another Vanderbilt report that currently issues as unstructured text,
so Levy is weighing solutions for getting it into structured form.
As for structured cancer staging data, Vanderbilt’s electronic medical
record system already has a module that oncologists can use to
enter this information. But not everyone uses it.
“We have to work on that, so that clinicians understand that,
if they put it in, they get this secondary gain,” Levy says. Perhaps
most challenging will be to gather information on side effects like
nausea and diarrhea, information currently adrift in clinical notes
written by physicians and nurses; one possibility is natural language
processing, which works by text mining and keyword identification.
The system will also need to know various patient preferences
(a grim real-world example: would the patient prefer hair
loss or diarrhea with his chemo?).
Beginning in July 2011, Levy plans to start rolling out a cancer
decision-support-cum-ordering system, covering chemo, targeted
drugs, labs and imaging – and spanning inpatient, outpatient
and home medication realms.
As standardized assessment kicks in and the system starts to
learn, it won’t be left to evolve entirely on its own. Guidance for
best practice, especially regarding drugs, is the province of the
pharmacy and therapeutics committee.
“This will be an enhancement and escalation of complexity in
terms of the types of data that drive the committee,” Masys says,
“but the fundamental combination of people, process and technology
are all there – just need to pour in the new data.”
As the system matures, at some point it will become appropriate
to push some of the decision support features directly to patients.
Acquiring the types of personal genomic data required to do
this used to be cost-prohibitive; it initially cost billions of dollars
to sequence the human genome.
“Now, to actually get the complete sequence of a cell, it’s in
the range of about $20,000 to $50,000,” Masys says, “and we
think, with so-called next generation sequencing technologies, that
within three to five years you could get your entire genome in your
electronic medical record for less than the price of a CT scan, for
about $1,000.”
We may be giving drugs to computers sooner than we
thought.
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800 1000
A
CLICK
AWAY
Social media connects a cancer community
Ilana Horn first discovered Facebook in 2006 after her brother
died of a rare form of prostate cancer at only 36.
In her search for photos, his friends directed her to a memorial
page on the social networking site that connects family and
friends.
“At that time of great grief, it was very important to have the
support and love of so many people, near and far,” Horn says.
After that, the associate professor of mathematics education at
Vanderbilt’s Peabody College says she became an “avid Facebooker”
and dabbler in Twitter, a “micro-blogging” service that allows
exchange of short, 140-character updates similar to text messaging.
Since being diagnosed with her own breast cancer, Horn has
found social media to be a helpful tool to connect with other
young adults she thinks of as cancer “fighters” and “survivors.” She
blogs and “tweets” as Chemo Babe (@chemo_babe).
“There are so many things that are difficult about facing cancer,”
she says. “It takes persistence and courage. I don’t always feel
that way, but I kind of hold Chemo Babe up as a warrior who can
take her knocks and get back up ready to keep fighting.”
Social media, including Twitter, Facebook, MySpace and
YouTube, allows for connecting and sharing of “user-generated
content” made possible because of new Web-based technologies. In
.10 03.01.10 04.01.10
some circles, it is seen as a revolution in the way that communities
develop, people communicate, and how consumers and organizations
or brands relate to each other.
Online communities for cancer survivors are nothing new.
The non-profit Association of Cancer Online Resources, ACOR,
was established in the mid-1990s to offer a collection of online
communities for those impacted by cancer and related disorders.
The founder, Gilles Frydman, discovered the need for such outlets
when his wife, Monica, was diagnosed with breast cancer and he
turned to the Internet to find information.
In some ways, social media is simply the current expression of
patient activation and engagement, according to Susannah Fox, a
researcher with the Pew Internet and American Life Project. But
today, the group that Fox calls “e-patients” are part of a larger cultural
change that “assumes access to information, enables communication
among disparate groups, and expects progress,” Fox wrote
in a January commentary.
Research that Fox reported last summer found that nearly
two-thirds of Internet users went online seeking health care information.
In addition, one-third of American adults are caregivers
for a loved one, and eight in 10 of those folks go online.
“One-third of adults experienced a medical emergency in the
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30
3500
3000
2500
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2000
1500
1000
500
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18-24
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35-44
45-54
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800 1000
Since the Cancer Center’s Facebook page was launched in October
2009, more than 3,000 people have become “fans,” with females age
35-44 as the largest demographic.
Fan growth
Fan demographics
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female
female
3,131
as of 4/15/10
male
male
past year, either their own or someone else’s. They are online too,”
her January commentary noted. “A medical crisis flips a switch in
people. It makes them want to become superheroes and save a life
if they can. The Internet is very often their weapon of choice.”
For cancer survivors, social media is nothing less than a “game
changer,” says Matthew Zachary, founder of I’m Too Young for
This, a foundation dedicated to assuring that young adult cancer
survivors receive age-appropriate treatment and support.
“Social media are enabling people to make smarter decisions
and have access to trusted, credible, peer-reviewed sources of information,”
said Zachary, who tweets as @stupidcancer.
Organizations who are doing it well are marrying offline and
online activities to share information, he says, citing Planet Cancer
as one organization that has successfully embraced social media in
its outreach, again to young adult cancer survivors. Its founder,
Heidi Adams, has a regular video blog as part of its multi-media
website, www.planetcancer.org.
But social media is not just the domain of the young. The
fastest-growing group of Facebook users is women in middle age.
With the average age of onset of cancer at 67, that is making social
media an increasingly attractive arena for centers like Vanderbilt-
Ingram Cancer Center to reach survivors, families, newly diagnosed
patients, prospective donors and others.
As one example, Vanderbilt-Ingram Cancer Center uses both
Facebook and Twitter to provide cancer education, celebrate survivors
and advocate for the research that will make a difference in
this set of diseases.
Lola Butcher, a reporter for the trade publication Oncology
Times, has written about the use of social media by oncologists
and cancer centers. She says that she is seeing more and more cancer
centers and support organizations embracing social media as an
opportunity to communicate in new ways with new audiences.
“Because many forms of social media cost little or nothing,
the advent of blogging and fan pages and Twitter and virtual
communities has let organizations with tight marketing or media
budgets raise their profile with specific audiences,” says Butcher,
whose Twitter “handle” is @lolabutcher.
“It’s neat to watch how cancer centers build their ‘brand’ by
the way they present themselves on Twitter and Facebook – very
humanizing! My reporting found that not-for-profit organizations
are actually ahead of corporations in their use of social media,
and some of the big-name cancer organizations are leaders in this
phenomenon.”
Another trend, she says, is use of Twitter and other social
media to share research findings, either published or presented at
meetings.
13-17
18-24
25-34
35-44
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3000
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2000
03.01.10 04.01.10
Ilana Horn –
Chemo Babe Blog:
http://chemobabe.com
Twitter handle: @chemo_babe
Matthew Zachary –
I’m Too Young for This Web page:
http://i2y.com/
Twitter handle: @stupidcancer
Lola Butcher –
Twitter handle: @lolabutcher
Planet Cancer:
www.planetcancer.org
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1000
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“When I interviewed Dr. Raymond DuBois (former director
of Vanderbilt-Ingram Cancer Center and immediate past president
of the American Association for Cancer Research) he said he had
become aware of research findings through Twitter that he would
likely have missed otherwise.”
Both Zachary and Butcher say that cancer centers have a long
way to go to reach the potential that social media offers for them
and for their patients and families.
“The online presence of marketing and communications staff
from centers is great because it positions the centers as friendly,
warm and helpful organizations,” Butcher says. “But what centers
have to offer ultimately are the physicians and researchers who
work there, so getting them online is pretty important.”
Zachary suggests, however, that privacy regulations may make
it difficult for hospitals, cancer centers and oncologists to use
social media to develop communities and urges intelligent partnerships
with advocacy and other organizations.
Butcher also notes that the complexity of the physicianpatient
relationship is a challenge online. “Some of the pioneering
physicians in social media are discussing the ethical issues regarding
patients and potential patients who contact them on social networking
sites, and I expect some norms and standards for what
constitutes appropriate physician/patient interaction online will
emerge fairly soon.”
Horn suggests that social media may offer opportunities to
deliver dynamic patient education that meets needs on a more
individual basis. And there’s no substitute for survivors educating
each other, she says.
“When this battle is being waged on your body, it can feel
relentless,” she says. “It is a psychic relief to connect with others
experiencing the same thing. Some are ahead of you and can offer
advice and guidance. Some can benefit from your hard-earned wisdom.
But a lot of what we do is root for each other and try to pick
each other up when we are down.”
Editor’s note: Connections to each of the sources included in this article
were made through online relationships.
Social rules
At Vanderbilt University Medical Center, a team representing
marketing, communications, nursing, physician leadership,
legal, privacy, patient advocacy and other concerns spent
several months crafting a social media policy to guide
engagement for faculty and staff in social media as well as to
set ground rules for the public engaging on VUMC-hosted
sites. Policies, guidelines and tips for using social media
more effectively are posted on the VUMC website
(www.mc.vanderbilt.edu).
Vanderbilt has been a leader in developing its patient portal,
MyHealthatVanderbilt.com, which allows for secure access to
medical records and e-mail interaction with patients’ medical
teams that is included in the medical record. Vanderbilt’s
policy currently calls for direct physician-patient interaction
to occur in that environment, but patients, families, and
“fans” are encouraged to connect with the Medical Center
and components like Vanderbilt-Ingram Cancer Center on
Facebook and Twitter. YouTube is increasingly being used to
share video content, and additional approaches to engage
and interact with the public and with patients are continually
being developed.
web link
To join the Vanderbilt-Ingram online community, find us on
Facebook (www.facebook.com/VanderbiltIngram)
and Twitter (twitter.com/ManleyatVICC).
31
Association of Cancer Online
Communities: www.acor.org
The E-Patients Blog:
http://e-patients.net
Pew Internet and American Life
Project: www.pewinternet.org
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STORIESOFSURVIVAL
MICHELLE ECKLAND
In Her Own Words
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Opposite page:
Michelle Eckland carries a piece of family history
around her neck. She wears her mother’s wedding
ring, which she recently found out had been handed
down from her great-grandmother, on a necklace. The
ring is estimated to be about 100 years old.
“Ohana means family. Family
means nobody gets left
behind – or forgotten.”
– from the animated movie Lilo & Stitch.
Afew years ago, “ohana” – for me – basically
meant my mom, my dad and my brother. Since
losing my mother to a rare form of cancer,
“ohana” has come to mean much more.
As a child, I was constantly afraid that one day I would wake up and
my mom would be dead. I remember in seventh grade waking up to my
brother telling me that my mom was in the hospital yet again. She had
multiple diseases that led to hospital visits, surgeries and numerous visits to
the doctors.
In my junior year of high school, my fear of losing my mom was
intensified. In April 2006, mom was diagnosed with stage 4 cholangiocarcinoma
– a rare cancer of the bile ducts. The doctors told her that her cancer
had a very poor prognosis and that she would probably live for about a
year. They told her that she could try chemotherapy but that it probably
wouldn’t shrink the size of her tumors. My mom started chemotherapy on
September 11, 2006 – just two weeks into my senior year of high school.
Throughout the next six months, as my mom received chemotherapy,
I watched her independence slowly diminish. First, she could no longer
drive. After that, the cancer took away her balance, her memory, and
everything that made my mom who she was. With each new development,
my fear would increase.
Every morning, I would wake up and make sure that she was still here
in my life, alive. Before school, I would go into her bedroom and give her
a kiss on the cheek. She would wake up for a second, smile, say “I love
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you,” and then fall right back to sleep. I wanted to make sure that if
my mom died while I was gone that she would know that I loved
her – and that I would know that I kissed her right before I left.
Throughout all of this, I was trying to live my life as a high
school senior. I applied to colleges, held numerous leadership positions
at my high school, and worked part-time. Looking back, I now
recognize how alone I felt. I didn’t have any friends who had a parent
with cancer; I felt like no one understood what I was going through.
In March 2007, the doctors stopped my mom’s chemotherapy
as it was no longer proving to be beneficial. But my mom held on
long enough to see me graduate from high school, hear my graduation
speech, and celebrate my 18th birthday with me.
My mom’s health really began to decline that summer. She
slowly became more swollen and forgot how to perform daily
functions. Worst of all, she had trouble remembering who I was.
On Aug. 2, 2007 – the day after her 50th birthday – I rode
in the ambulance with my mom as we moved her to a nursing
home. As tears streamed down her face, it suddenly hit me: my
mom was never going to see my house again. Instead she was
going to die in this nursing home where all of the patients
appeared twice her age.
At 6:48 a.m. on August 8, I awoke to my father shaking me.
He had just returned from my mom’s nursing home – and told me
that mom had passed away 10 minutes before he arrived there.
At first, I did not believe him. I was hurt and angry because
the hospice nurses were supposed to let us know when she was supposed
to pass. They said that she had at least a few more weeks to
live. I did not understand. I could not believe that I would never be
able to hug my mom again or kiss her and tell her that I love her.
My mom’s funeral was my first funeral. I didn’t know what to
expect. I didn’t know that the family went to the funeral home in
the morning before the funeral mass. After we said our goodbyes at
the funeral home, we sat in the limo and waited for them to roll my
mom’s casket to where it would be placed in the hearse. I watched as
these men slowly transported the casket from the church to the
hearse, and I thought, “my mom can’t possibly be in there.”
I didn’t know that, after we arrived at the church, my dad, my
brother, and I would have to walk behind the casket. As we walked
down the aisle with my dad in the middle – one arm around me,
the other around my brother – I remember realizing that “this is it,
this is my family now.” My mom was in the casket that was slowly
moving in front of me. She really was never coming back.
After my mom’s death, I did not know what to do with myself.
I did not want to sit around and cry all day – mom would not want
me to do that. However, everything I saw reminded me of her and
how she was no longer here. I wanted just to curl up in a ball and
hope that if I prayed hard enough that maybe she could come back.
I was told that I was supposed to grieve. I was not expected
back at work, and I was leaving for college at Vanderbilt University
in less than two weeks. I had not started my dorm shopping, and I
wasn’t even sure if I wanted to go to school for the fall semester.
But one conversation kept playing back in my head.
Earlier that summer, my mom sat me down on the couch
next to her. She told me that regardless of how she was doing, she
wanted me to go to school on time, and that knowing that I was
at school getting closer to my dream would put a smile on her
face. My dad always tells me that my mom passed when she did
because she wanted me to go to college more than anything.
Below:
Left: Anticipating the effects of chemo, Michelle had cut her hair off to
donate for “Locks of Love” in case her mother, Kathy, lost hers during
treatment.
Right: Michelle says her mom was “jealous” of her stuffed heffalump (a character
from Winnie the Pooh). “So I went to the Disney store and got her a
baby one. She used to bring hers to the hospital…She’s buried with that, and
I still have mine and sleep with it every night.”
S P R I N G 1 0 • m o m e n t u m

S T O R I E S O F S U R V I VA L
So I knew what I had to do, but I did not know how I would
be able to survive.
Move-in day at college amplified my loneliness and pain.
Here I was, an 18-year-old girl who had just lost my mother, and
while I was unpacking my things and trying to organize my room,
some of the other girls (in the dorm) were complaining about how
annoying their moms were and how they couldn’t wait for their
moms to leave so that they could decorate their rooms the way
they wanted to.
I felt so alone and had absolutely no idea how I was going to
survive in this new environment 1,100 miles away from my family
back home in Massachusetts.
A few days into the semester, I became an emotional wreck; it
was right around the one-year anniversary of when my mom started
chemo. I visited the counseling center at Vanderbilt and met
with a therapist, who gave me a pamphlet on this place called
Gilda’s Club – which is a support community for people with cancer
and their families and friends.
I had never heard of the organization, and, honestly, I thought
my therapist was a little crazy and trying to pawn me off on someone
else. I thought, “if this was such a great organization why had
I never heard of it” and “why was there not one in Massachusetts
where there are some of the best hospitals in the country?”
I followed my therapist’s advice and one day went to a new
member meeting at Gilda’s Club. At the time, there were no support
groups that dealt with the loss of a parent, and I found it
challenging to even get to the clubhouse. But, towards the end of
my first semester, as I really started to struggle with my mom’s
death, I learned about Gilda’s Gang – a program started by a
Gilda’s Club member (Gail Addlestone, M.D.) who died of breast
cancer in 2007. The “gang” combines volunteer fundraising with a
16-week course of fitness training, which culminates in the group
participating in the Country Music Half Marathon, held each
spring in Nashville.
I thought that it would be a great way to challenge myself and
to meet other people who had been affected by cancer.
So in January 2008 I joined Gilda’s Gang and started training
for the Country Music Half Marathon – having never run a mile
in my life.
For the next 16 weeks, I would wake up at 6:15 a.m. every
Saturday and walk over to Gilda’s Club to be ready for our 7 a.m.
long runs. I remember during some of our runs how much I would
struggle, and I would question why in the world I was running 10
miles at 7 a.m. on a Saturday morning. But then I would remember
my mom, how strong she was and how she fought for so long.
When I crossed the finish line, I was nearly in tears. My mom
would’ve never believed I ran one mile not to mention 13.1 miles.
I had done it all for her and to raise money for Gilda’s Club,
which had helped me so much throughout that stressful year.
I decided to participate in Gilda’s Gang again in 2009 to give
back to this organization that was becoming a huge part of my life
– and an extension of my family. I had another incredible experience
with the team – even though my friends still think I’m crazy
Team Moe
Michelle and cancer survivor Maurice (“Moe”) Mantus at Gilda’s
Club Nashville. On Saturday, April 24, Michelle and the rest of
“Team Moe” completed the Country Music Half-Marathon. To see
Moe’s story and the race results, check out our special online feature
at www.vicc.org/momentum. (Photos by Joe Howell)
35
m o m e n t u m • S P R I N G 1 0

S T O R I E S O F S U R V I VA L
36
So many things in life are out of my control.
But helping Moe complete this race is one thing that I can do
so that a new member of my “family” doesn’t get left behind…
and so that my mom will never be forgotten.
In her dorm room, Michelle keeps a variety of mementos of her mother on
her bed – including several heffalumps and a “World’s Greatest Mom”
Minnie Mouse she had given her mom as a gift.
S U SAN U R M Y
for waking up at 6:15 a.m., and my roommate doesn’t really
appreciate it.
A couple of weeks after the 2009 half-marathon, I was in the
glass-painting group (one of the best groups at Gilda’s that has
some of the sweetest members in it) and there were several Gilda’s
Gang participants in the room. As we talked about how much fun
we had with the Saturday morning runs, how we loved getting to
know other members of the Gang, and how much fun the actual
half-marathon was, an older man – whom I had never met – came
in. His name was Moe Mantus. I learned he had been training for
a half-marathon prior to his cancer diagnosis. He talked about
how much he loved running, how he had previously done halfmarathons,
and how it was his dream to do another one. He
talked about how now he wouldn’t be able to do a half-marathon
on his own since he can only walk short distances.
Immediately I volunteered myself to push him in a wheelchair
for the half-marathon, and one of the staff members agreed that it
could happen. Why I, a college student, agreed to push a man
twice my size in a wheelchair 13.1 miles is beyond me, but I guess
that it is kind of representative of my personality. I’ve spent the
past few months working on finding a wheelchair and organizing a
team to help me push Moe. We have been training with the
“gang” on Saturday mornings, and I now have a greater awareness
of all of the hills in Nashville.
Gilda’s Club Nashville has provided me with more love and
support than I ever thought possible. The members and staff have
truly become my family. I know that anytime I need a hug, I can
walk through the club’s signature red doors, and there will be at
least 10 members with open arms ready to hug me.
Many of the women here remind me of my mom through
their personalities, laughter and gentleness. There is now a “young
adults grieving the loss of a parent group,” and over the past yearand-a-half
I have grown close to the girls in my group. Twice a
month I am able to talk about what it’s like to lose a parent to a
group of people who completely understand.
So that quote from Lilo & Stitch really resonates for me, now
more than ever. Gilda’s has become my family; therefore, Moe has
become part of my family.
So many things in life are out of my control. But helping Moe
complete this race is one thing that I can do so that a new member
of my “family” doesn’t get left behind…and so that my mom will
never be forgotten.
S P R I N G 1 0 • m o m e n t u m

quicktakes
Q U I C K TA K E S
Cancer Center team grows
The Vanderbilt-Ingram Cancer Center
team of researchers, physician-scientists and
clinicians continues to grow. Faculty who
joined Vanderbilt-Ingram in 2009 include:
37
Cancer Center investigators land
Stand Up to Cancer grant
William Pao, M.D., Ph.D., associate professor
of Medicine, has been awarded a
grant from Stand Up to Cancer (SU2C) to
identify molecules that could speed the
search for new cancer drugs and targets.
He is one of 13 young cancer investigators
to earn a grant from SU2C. Over a threeyear
period, each investigator will receive
up to $750,000 from SU2C’s Innovative
Research Grants program, which supports
the next generation of cancer researchers.
Pao and his colleagues are studying
kinases, molecules inside cells involved in
telling a cell whether to proliferate. In cancers,
these kinases can become aberrant so
that they are stuck in the “on” position,
telling cells to divide all the time.
“Mutant kinases are very druggable targets,
so if you identify the right drug to turn
off a specific mutant kinase in cancer, you
can kill the tumor,” said Pao, Ingram
Associate Professor of Cancer Research and
director of Personalized Cancer Medicine.
The best example of this is in chronic
myelogenous leukemia (CML), caused by an
abnormal fusion of the kinase ABL with
another protein (BCR). The discovery of that
kinase fusion led to the drug Gleevec, which
revolutionized treatment for CML.
Pao and graduate student Juliann
Chmielecki have found a way to speed up
William Pao, M.D., Ph.D., left, with colleagues, from
left, Peilin Jia, Ph.D., Juliann Chmielecki and
Zhongming Zhao, Ph.D.
the search for fusions involving any of the
90 tyrosine kinases in the human genome,
using minimal amounts of starting tumor
material.
The team – which includes Zhongming
Zhao, Ph.D., associate professor in
Biomedical Informatics, and Peilin Jia, Ph.D.,
research fellow in Biomedical Informatics –
is now ready to start screening tumors for
novel fusions.
Pao said this focus on genetic profiling
of tumors will lead to improvements in personalized
medicine.
“Many drug companies are developing
kinase inhibitors, so there may already be a
drug in development that would target a
fusion that we find,” said Pao. “We could
then prioritize patients who should receive
that drug, based on the genetic profile of
their tumor.”
This is the Cancer Center’s second
SU2C grant. Earlier this year, Carlos Arteaga,
M.D., director of the Vanderbilt-Ingram
Breast Cancer Program, and Patty Lee, Patient
Research Advocate, were chosen to participate
in one of the SU2C Cancer Dream
Teams studying breast cancer.
– by Dagny Stuar t
MARY D O N AL D S O N
Vandana Abramson, M.D. – breast oncology
Dana Backlund, M.D. – gastrointestinal oncology
James Broome, M.D. – endocrine surgery
Scott Borinstein, M.D. – pediatric oncology
Dai Chung, M.D. – pediatric surgery
Sandra Deming, Ph.D., M.P.H. – epidemiology
Stephen Fesik, Ph.D. – leading Cancer Drug
Discovery
David Gius, M.D., Ph.D. – radiation oncology
Leora Horn, M.D. – thoracic oncology
Mia Levy, M.D. – chief medical informatics
officer
Eric Liu, M.D. – surgical oncology
Kevin Palka, M.D. – neuro-oncology
William Pao, M.D., Ph.D. – leading Personalized
Cancer Medicine Initiative
David Penson, M.D., M.P.H. – urologic surgery
Otis Rickman, D.O. – pulmonology
Allen Sills, M.D. – neurological surgery
Stephen Smith, M.D. – oncology, Cool Springs
practice
William Tansey, Ph.D. – co-leading the Genome
Maintenance Program
Zhongming Zhao, Ph.D. – chief bioinformatics
officer
New call center streamlines access
for Cancer Center patients
The Vanderbilt-Ingram Cancer Center
has created a new call center designed to
streamline access for both patients and
referring providers, including local
(Davidson County) and toll-free numbers.
• Patients seeking an appointment or needing
to reach the cancer clinics: 936-VICC
(936-8422) or 877-936-VICC (877-936-
8422)
• Referring clinicians seeking to make a
referral or schedule a consultation: 343-
3700 or 877-6MD-VICC (877-663-8422)
• Both patients and referring clinicians
seeking additional information or access
to a cancer clinical trial: 936-5847 or 800-
811-8480
m o m e n t u m • S P R I N G 1 0

Q U I C K TA K E S
38
During the holidays, a quartet from the Nashville
Symphony (from left, Deidre Bacco, Anna Lisa
Hoepfinger, Dan Reinker and Dawn Hartley)
played Christmas carols and other holidaythemed
music in the Chemotherapy Infusion
Clinic and outside the Cancer Clinic reception
lobby.
AN N E R AY N E R
Nashville Symphony brings soothing
sounds to Vanderbilt-Ingram
The rich sounds of violins and other
stringed instruments are resonating
through the halls of the Vanderbilt-Ingram
Cancer Center.
After months of planning, Nashville
Symphony members are volunteering their
time to bring orchestral music to cancer
patients and their families.
“The Symphony approached
Vanderbilt-Ingram Cancer Center because
our music is ultimately about serving our
communities and those with the most
need,” said Mitchell Korn, the symphony’s
vice president for education and community
engagement. “Our musicians are dedicated
to providing music in all kinds of settings,
and here we are given the privilege to
create music and beauty for those who are
amidst real struggle.”
Musicians who offer to play at
Vanderbilt University Medical Center must
go through the same training required for
all hospital volunteers.
“We wanted to bring another form of
music to our patients, so we set up a special
training session to accommodate the
tor of the REACH for Survivorship Program,
a collaborative venture between the
Department of Pediatrics, the Monroe Carell
Jr. Children’s Hospital at Vanderbilt and the
Cancer Center.
“Our programs in pediatric cancer are
our highest priority, and I am truly delighted
with this choice,” said Jonathan Gitlin, M.D.,
assistant vice chancellor for Maternal and
Child Health and chair of the Department of
Pediatrics. “Deb Friedman is an extraordinary
individual who will lead the division
with compassion and creativity.”
Friedman came to Vanderbilt in 2008
from Seattle, where she was director of the
LiveStrong Survivorship Center of
Excellence at the Fred Hutchinson Cancer
Research Center and director of the Cancer
Survivorship Program at Children’s Hospital
complicated schedules of these musicians,”
said Kim Hunter, program coordinator of
Patient and Family Support Services for
Vanderbilt-Ingram.
Fifteen members of the Nashville
Symphony have already been trained as
volunteers, and small groups of the musicians
will be playing in parts of the Cancer
Clinic as their schedules allow.
Some of the musicians have a personal
reason for volunteering. The Schermerhorn
Symphony Center in downtown Nashville
was named in honor of the late Maestro
Kenneth Schermerhorn, who led the
Grammy Award-winning Nashville
Symphony for 22 years. He died of non-
Hodgkin’s lymphoma in 2005.
“This place means a lot to us because
our former music director was here,” said
Deidre Bacco, one of the first violinists.
“When I think of Vanderbilt-Ingram, I think
of Maestro (Kenneth) Schermerhorn, and it
is a way to give back to his memory.”
– by Dagny Stuar t
Friedman to
lead Pediatric
Hematology/
Oncology
Debra
Friedman, M.D.,
was recently
named the director
of the Division of
Pediatric Hematology/Oncology at
Vanderbilt University following an extensive
national search.
Friedman, associate professor of
Pediatrics and the E. Bronson Ingram Chair
in Pediatric Oncology, served as interim
director since July 2009.
Friedman is the leader of the Cancer
Control and Prevention Program at the
Vanderbilt-Ingram Cancer Center and direcand
Regional Medical Center.
“Having a world-renowned expert
such as Dr. Friedman as both a leader of
our cancer control and survivorship
research as well as director of clinical care
and research in pediatric hematology/oncology,
assures a collaborative and
integrated approach that is critical as we
move forward,” said Jennifer Pietenpol,
Ph.D., director of the Cancer Center.
“It is an incredible honor,” Friedman
said. “I am so fortunate to work with an
exceptionally dedicated and talented faculty
and staff. I look forward to working with
all of them to advance our clinical and
research enterprise to improve the lives of
children and their families living with,
through and after cancer.”
– by Jessica Ennis
S P R I N G 1 0 • m o m e n t u m

Q U I C K TA K E S
New pet visitor team has strong
Vanderbilt roots
Vanderbilt-Ingram Cancer Center’s
newest pet visitor team – a miniature
Australian labradoodle named Maddie and
her human friend, Allan Bass Jr. – is bringing
smiles to the faces of cancer patients
and families.
“My wife’s priorities for a dog were
simple: no shedding and a relatively small
size,” said Bass. “My priority was a
Labrador retriever.”
So the Nashville couple settled on a
puppy with a mixture of poodle and
Labrador traits –evident in Maddie’s silkysoft
fur and happy demeanor.
When Bass decided he should share
Maddie’s loving disposition with others, he
immediately thought of Vanderbilt
University Medical Center.
His wife’s breast cancer was treated by
physicians at Vanderbilt-Ingram. His father,
Allan D. Bass, M.D., now deceased, was
chair of the Department of Pharmacology
for two decades and served as acting dean
for Biomedical Sciences during 1973-74.
And Bass’ mother, Sara, was a graduate of
the Vanderbilt University School of Nursing.
“My parents molded me and taught me
to do things for others,” said Bass. “They
told me that only about 10 percent of people
make the world go around.”
So he has focused on being one of the
10 percent who make a difference, and he
decided Maddie could help.
He and Maddie enrolled in a Delta
Society-sponsored pet partners program,
which trains human-animal teams for visiting
animal programs in hospitals, nursing
homes and schools. Every pet visitor team
at Vanderbilt must undergo this rigorous
training, and Bass and Maddie received
theirs through Nashville-based Therapy
ARC.
With their Delta Society certification
under their collars, the duo started visiting
nursing homes and recently added
Vanderbilt-Ingram to their circuit.
Whether it’s Maddie’s beautiful brown
eyes, Bass’ soothing voice, or some combination
of the two, the new team is already
winning friends among the Cancer Center’s
staff and patients.
– by Dagny Stuar t
Patient Patricia Hollins spends a little quality time
with Vanderbilt-Ingram Cancer Center’s newest
pet visitor team, Allan Bass Jr. and ‘Maddie.’
AN N E R AY N E R
Lung cancer trial goes online for
‘never smokers’
A new study is harnessing the power of
the Web to help search for genetic differences
that may help explain why some
“never smokers” develop lung cancer.
More than 219,000 people are diagnosed
with lung cancer in the United States
every year, according to the National Cancer
Institute. About 20,000 – one in 10 – never
smoked, and most are women.
“Our goal is to look at the DNA in blood
or saliva samples as part of a future genomewide
association study,” said William Pao,
M.D., Ph.D., director of Personalized Cancer
Medicine at Vanderbilt-Ingram Cancer Center,
and lead investigator on the study.
Pao and colleagues hope to collect
2,000 DNA specimens from never smokers
(individuals who have smoked fewer than
100 cigarettes in their lifetime). Since a single
cancer center sees so few of these types
of patients each year, Pao turned to the Web
to recruit patients.
Patients fill out a Web-based questionnaire
and, if they qualify, are sent two empty
blood vials. The vials can be filled at their
next doctor’s visit and shipped to Vanderbilt
via UPS (postage paid). Those who can’t get
blood drawn may provide saliva samples. To
protect patient privacy and to prevent tracing
samples back to a specific donor, the
DNA samples are de-identified.
According to the American Cancer
Society, fewer than 20 percent of lung cancer
patients are still alive five years after
diagnosis.
“More than half of all lung cancer
patients are diagnosed in the incurable
stage, so we’re already on the losing side of
the battle with too many patients by the
time we detect the cancer,” explained Pao,
who is also an Ingram Associate Professor of
Cancer Research.
“Eventually, this kind of study may help
us identify genetic targets that allow us to
develop simple blood tests to detect cancer
early. Those same targets could be used to
develop drugs that block or interfere with
the disease process.”
– by Dagny Stuar t
web link
Visit www.vicc.org/neversmokers for more information.
39
m o m e n t u m • S P R I N G 1 0

J O U R N A L WAT C H
40
JOURNAL WATCH
Vanderbilt-Ingram Cancer Center is committed to conducting innovative,
high-impact basic, translational and clinical research with the
greatest potential for making a difference for cancer patients, today
and in the future. Here’s a sampling of recent work published in peerreviewed
journals by center investigators:
Protein suppressor of colon tumors
In the March 1 Journal of Clinical Investigation, James Goldenring, M.D.,
Ph.D., and colleagues report that expression of Rab25 – a protein
known to regulate protein trafficking within the cell – may play a role in
early colon tumor development. The investigators found substantially
decreased Rab25 expression in human colorectal tumors compared
with normal colon and that lower Rab25 expression levels predicted
poorer survival. To clarify Rab25’s role in colorectal tumor formation,
the investigators generated mice lacking Rab25 and found that Rab25-
deficient mice developed more intestinal polyps and colon tumors than
parental mice. The findings suggest that Rab25 may act as a tumor suppressor
in the colon lining and that reduction of Rab25 expression may
be an early event in colon cancer formation.
Gene signature for colon cancer prognosis
R. Daniel Beauchamp, M.D., and colleagues have identified a gene signature
that may help identify patients at risk of colon cancer recurrence
– and identify patients most likely to benefit from chemotherapy.
From a 300-gene expression signature initially identified in mouse
colon cancer cells, the investigators developed a 34-gene signature
most closely associated with metastasis and death (in a set of
Vanderbilt patient samples). In a larger patient population, they found
that patients with the “poor prognosis” signature – the expression pattern
seen in highly invasive mouse cells – were five times more likely
to have a cancer recurrence than those with a “good” prognosis signature.
Also, stage III patients with the “poor prognosis” signature
appeared to benefit from chemotherapy whereas those with the
“good prognosis” signature showed little benefit. The findings, published
in the March issue of Gastroenterology, could help personalize
treatments for colon cancer.
Protein protector against DNA stress
Genome maintenance systems prevent and repair DNA damage to
maintain the genome’s stability and protect against mutations that
cause cancer and other diseases. In their search for novel genome
maintenance factors, David Cortez, Ph.D., and colleagues have identified
SMARCAL1 as a genome maintenance protein. Mutations in
SMARCAL1 are known to cause the rare genetic disorder Schimke
immunoosseous dysplasia (SIOD), but the function of SMARCAL1
and its mechanistic role in the disease have remained unclear. In the
Oct. 15 Genes & Development, the researchers report that SMARCAL1
protein acts to limit DNA damage at stalled replication “forks” (sections
of unwound DNA undergoing replication). The findings suggest
that mutations in SMARCAL that result in defective cellular responses
to replication stress may at least partially explain the variety of
symptoms associated with SIOD.
Drugs join forces to overcome lung cancer resistance
William Pao, M.D., Ph.D., and colleagues have found that combining
two targeted cancer therapies may overcome resistance of lung cancers
to Iressa and Tarceva – drugs that initially work well against lung
cancers with mutations in the epidermal growth factor (EGF) receptor
but lose their effectiveness over time. About half of drug-resistant
lung tumors harbor a new mutation (called T790M) in the EGF receptor.
The researchers found that mouse tumors with the T790M mutation
did not respond to Iressa, Tarceva, an experimental EGF receptor
inhibitor (BIBW-2992), or Erbitux – an antibody that blocks the interaction
of EGF receptor binding proteins with the EGF receptor.
However, the combination of Erbitux and BIBW-2992 effectively
“melted away” T790M-containing tumors. The results, in the Oct.1
Journal of Clinical Investigation, suggest a way to overcome T790Mmediated
resistance and support moving forward with clinical trials
in patients with lung cancer.
New target for severing cancer’s access to supplies
Charles Lin, Ph.D., and colleagues have identified a protein – deltacatenin
– involved in blood vessel development (angiogenesis) during
disease conditions, but not during normal physiological processes.
They found that endothelial cells from mice missing delta-catenin had
reduced motility and vascular structure formation, compared to cells
from normal mice. And in models of tumor growth and wound healing,
mice missing delta-catenin showed reduced tumor growth and
blood vessel density and impaired angiogenesis and wound closure.
In contrast, these mice had normal physiological hormone-induced
angiogenesis in the uterus. The findings, reported in the January
Journal of Experimental Medicine suggest that delta-catenin may be a
promising therapeutic target for blocking blood vessel growth in disease
conditions like cancer.
Food, exercise, blood type and cancer
Two studies on breast cancer survivors in Shanghai, China, have
revealed dietary and lifestyle factors that influence cancer risk and
quality of life. In a study published in the Dec. 9 Journal of the
American Medical Association, Xiao Ou Shu, M.D., Ph.D., and colleagues
found that women who reported the highest soy food intake
had the lowest breast cancer mortality and recurrence rates compared
with women in the lowest soy food intake group. And in the
January Journal of Clinical Oncology, they reported that breast cancer
patients who exercise and drink tea on a regular basis may be less
likely to suffer from depression than other patients.
web link
More information about our research at:
www.vicc.org/research
S P R I N G 1 0 • m o m e n t u m

onefinalnote
Busting myths about cancer clinical trials
Using elements of “Jeopardy,” “Saturday
Night Live” and the Discovery Channel show
“MythBusters,” Vanderbilt cancer survivors and
researchers have developed an entertaining program
to skewer myths about cancer clinical trials.
The educational project, “Mythbusters:
Cancer Research in Jeopardy,” was presented
recently by Vanderbilt-Ingram Cancer Center
Research Advocates and members of the
Vanderbilt Postdoctoral Association.
Patient Research Advocate Patty Lee (as
“Alexandra Trebek”) presented 10 common
myths about cancer research and clinical trials
and encouraged nearly 50 audience participants
to vote on possible answers electronically.
Videotaped answers from Vanderbilt cancer
experts were used to debunk the myths and provide
factual information about cancer clinical trials
available to patients today.
“The goal of this interactive program is to
dispel misconceptions associated with cancer
research and provide educational material in a
relaxed and entertaining environment,” said Jane
Kennedy, manager of Patient Advocacy, who
spearheaded the development of the program.
The educational project was also highlighted
at this year’s American Association of Cancer
Research 101st Annual Meeting.
– Dagny Stuart
A PANEL OF FAUX CELEBRITIES PARTICI-
PATE IN “MYTHBUSTERS: CANCER
RESEARCH IN JEOPARDY” AT A GILDA’S
CLUB NASHVILLE EVENT IN OCTOBER
2009. (FROM LEFT) CAROLINE HANSON
(AS MARTHA STEWART), GARY PIPER (AS
JIMMY BUFFET) AND PAM MARTIN (AS
DORIS GUMP). (PHOTO BY JOE HOWELL)