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

1132 Chapter 20: Cancer
Infectious Agents Can Cause Cancer in a Variety of Ways
In papillomaviruses, the viral genes that are mainly to blame are called E6 and E7.
The protein products of these viral oncogenes interact with many host-cell proteins,
but, in particular, they bind to two key tumor suppressor proteins of the host
cell, putting them both out of action and so permitting the cell to replicate its DNA
and divide in an uncontrolled way. One of these host proteins is Rb; the other
is p53. Other DNA tumor viruses use similar mechanisms to inhibit Rb and p53,
underlining the central importance of inactivating both of these tumor suppressor
pathways if a cell is to escape the normal constraints on proliferation.
In other cancers, viruses have indirect tumor-promoting actions. The hepatitis-B
and C viruses, for example, favor the development of liver cancer by causing
chronic inflammation (hepatitis), which stimulates an extensive cell division in
the liver that promotes the eventual evolution of tumor cells. In AIDS, the human
immunodeficiency virus (HIV) promotes development of an otherwise rare cancer
called Kaposi’s sarcoma by destroying the immune system, thereby permitting
a secondary infection with a human herpesvirus (HHV-8) that has a direct
carcinogenic action. By causing severe inflammation, chronic infection with
parasites and bacteria can also promote the development of some cancers. For
example, chronic infection of the stomach with the bacterium Helicobacter pylori,
which causes ulcers, appears to be a major cause of stomach cancer; dramatic
falls in the incidence of stomach cancer over the last half-century (see Figure
20–39) correlate with a decline in the incidence of Helicobacter infections.
The Search for Cancer Cures Is Difficult but Not Hopeless
The difficulty of curing a cancer is similar to the difficulty of getting rid of weeds.
Cancer cells can be removed surgically or destroyed with toxic chemicals or radiation,
but it is hard to eradicate every single one of them. Surgery can rarely ferret
out every metastasis, and treatments that kill cancer cells are generally toxic to
normal cells as well. Moreover, unlike normal cells, cancer cells can mutate rapidly
and will often evolve resistance to the poisons and irradiation used against
them.
In spite of these difficulties, effective cures using anticancer drugs (alone or in
combination with other treatments) have already been found for some formerly
highly lethal cancers, including Hodgkin’s lymphoma, testicular cancer, choriocarcinoma,
and some leukemias and other cancers of childhood. Even for types
of cancer where a cure at present seems beyond our reach, there are treatments
that will prolong life or at least relieve distress. But what prospect is there of doing
better and finding cures for the most common forms of cancer, which still cause
great suffering and so many deaths?
Traditional Therapies Exploit the Genetic Instability and Loss of
Cell-Cycle Checkpoint Responses in Cancer Cells
Anticancer therapies need to take advantage of some molecular peculiarity of
cancer cells that distinguishes them from normal cells. One such property is
genetic instability, reflecting deficiencies in chromosome maintenance, cell-cycle
checkpoints, and/or DNA repair. Remarkably, the most widely used cancer
therapies seem to work by exploiting these abnormalities, although this was not
known by the scientists who first developed the treatments. Ionizing radiation
and most anticancer drugs damage DNA or interfere with chromosome segregation
at mitosis, and they preferentially kill cancer cells because cancer cells have a
diminished ability to survive the damage. Normal cells treated with radiation, for
example, arrest their cell cycle until they have repaired the damage to their DNA,
thanks to the cell-cycle checkpoint responses discussed in Chapter 17. Because
cancer cells generally have defects in their checkpoint responses, they may continue
to divide after irradiation, only to die after a few days because the genetic
damage remains unrepaired. More generally, most cancer cells are physiologically
deranged to a stressful degree: they live dangerously. Even though the cells