Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

CANCER PREVENTION AND TREATMENT: PRESENT AND FUTURE
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RTK inhibitors
Trastuzumab
Gefitinib
Erlotinib
Cetuximab
Bevacizumab
B-Raf inhibitors
Dabrafenib
Vemurafenib
growth factor
P
P
P
P
P
P
B-Raf
receptor tyrosine kinase
Ras
GTP
Raf1
NF1
Raf inhibitors
Regorafenib
Sorafenib
Figure 20–44 Some anticancer drugs
and drug targets in the Ras–MAP-kinase
signaling pathway. Each of the signaling
proteins in this diagram has been identified
as a product of a cancer-critical gene, with
the exception of Raf1 and Erk. This Ras–
MAP-kinase signaling pathway is triggered
by a variety of receptor tyrosine kinases
(RTKs), including the EGF receptor (see
Figures 15–47 and 15–49). Those drugs
that are antibodies end in “mab,” while
those that are small molecules end in “nib.”
(Adapted from B. Vogelstein et al, Science
339:1546–1558, 2013.)
Mek inhibitors
Refametinib
Selumetinib
Trametinib
Mek
Erk
somewhere in the pathway can hopefully be found (Movie 20.7). As an example,
Figure 20–44 displays some of the anticancer drugs and drug targets that are currently
being tested for a pathway frequently activated in cancers.
MBoC6 n20.501/20.44
Many Cancers May Be Treatable by Enhancing the Immune
Response Against the Specific Tumor
Cancers have complex interactions with the immune system, and its various components
may sometimes help as well as hinder tumor progression. But for more
than a century it has been a dream of cancer researchers to somehow harness
the immune system in a controlled and efficient way to exterminate cancer cells,
just as it exterminates infectious organisms. There are finally signs that this dream
may one day be realized, at least for some forms of cancer.
The simplest type of immunological therapy, conceptually at least, is to inject
the patient with antibodies that target the cancer cells. This approach has had
some successes. About 25% of breast cancers, for example, express unusually high
levels of the Her2 protein, a receptor tyrosine kinase related to the EGF receptor
that plays a part in the normal development of mammary epithelium. A monoclonal
antibody called trastuzumab (trade name Herceptin®) that binds to Her2 and
inhibits its function slows the growth of breast tumors in humans that overexpress
Her2, and it is now an approved therapy for these cancers (see Figure 20–44). A
related approach uses antibodies to deliver poisons to the cancer cells. Antibodies
against proteins that are abundant on the surface of a particular type of cancer cell
but rare on normal cells can be armed with a toxin that kills those cells that bind
the antibody molecule.
A great deal of current excitement centers around a different type of approach,
based on the relatively recent recognition that the microenvironment in a tumor is
highly immunosuppressive. As a result, the cancer victim’s immune system is prevented
from destroying the tumor cells. Recall that, from the thousands of genome
sequences thus far determined, we know that a typical cancer cell will contain on
the order of 50 proteins with a mutation that alters an amino acid sequence, most
of these being “passenger” mutations, as previously explained (see p. 1104). Many
of these mutant proteins will be recognized by the patient’s immune system as
foreign, but—to allow the cancer cells to survive throughout the course of tumor
progression—the cancer cells have evolved a set of anti-immune defenses. These