Essential Cell Biology 5th edition

728 CHAPTER 20 Cell Communities: Tissues, Stem Cells, and Cancer
TABLE 20−2 EXAMPLES OF CANCER-CRITICAL GENES
Gene Class Effect of Mutation
Ras Proto-oncogene Activating mutations in Ras render the Ras protein continuously active, promoting
cell proliferation (discussed in Chapter 16)
β-catenin Proto-oncogene Activating mutations in β-catenin make the β-catenin protein resistant to
degradation, promoting cell proliferation (see How We Know, pp. 730−731)
p53 Tumor suppressor gene Inactivation of both copies of p53 allows cancer cells to continue to survive and
divide, even in the presence of damaged DNA (discussed in Chapter 18)
APC Tumor suppressor gene Inactivation of both copies of APC promotes excessive proliferation of cells in the
intestinal crypt (see Figure 20−52 and How We Know, pp. 730−731)
Brca1 and Brca2 Tumor suppressor genes Inactivation of both copies of Brca1 or Brca2 allows cancer cells to continue to
survive and divide in the presence of massively damaged DNA (discussed below).
Yet, in spite of these difficulties, an increasing number of cancers are
being treated effectively. Surgery remains a highly effective tactic, and
surgical techniques are continually improving: in many cases, if a cancer
has not spread far, it can often be cured by simply removing it. Where
surgery fails, the intrinsic peculiarities of cancer cells can be used against
them. Lack of normal cell-cycle control mechanisms, for example, may
help make cancer cells particularly vulnerable to DNA damage: whereas a
normal cell will halt its proliferation until such damage is repaired, a cancer
cell may charge ahead regardless, producing daughter cells that may
die because they inherit too many unrepaired breakages in their chromosomes.
Presumably for this reason, cancer cells can often be killed by
doses of radiotherapy or DNA-damaging chemotherapy that leave most
normal cells relatively unharmed.
diameter of tumor (mm)
100
10
1
0.1
death of
patient
(~10 ×
10 12 cells)
tumor first
palpable
(~10 × 10 9
cells)
tumor first
visible on X-ray
(~10 × 10 8 cells)
1 10 20 30 40
tumor cell population doublings
Figure 20–52 A tumor is generally not
diagnosed until it has grown to contain
hundreds of millions of cells. Here, the
growth of a typical tumor is plotted on a
logarithmic scale. ECB5 Years e20.54/20.56 may elapse before
the tumor becomes noticeable. The time
it takes for the number of cells in a typical
breast tumor to double, for example, is
about 100 days.
Surgery, radiation, and chemotherapy are long-established treatments,
but many novel approaches are also being enthusiastically pursued. In
some cases, as with loss of a normal response to DNA damage, the very
feature that helps to make the cancer cell dangerous also makes it vulnerable,
enabling doctors to kill it with a properly targeted treatment. Some
cancers of the breast and ovary, for example, owe their genetic instability
to the lack of a tumor suppressor protein (either Brca1 or Brca2) that
aids in the accurate repair of double-strand breaks in DNA (discussed in
Chapter 6); the cancer cells survive by relying on alternative types of DNA
repair mechanisms. Drugs that inhibit one of these alternative DNA repair
mechanisms specifically destroy the cancer cells by raising their genetic
instability to such a level that the cells die from chromosome fragmentation
when they attempt to divide. Normal cells, which possess an intact
double-strand break repair mechanism, remain relatively unaffected.
Another set of strategies aims to use the immune system to kill the tumor
cells. Antibodies that recognize tumor-specific cell-surface molecules can
be produced in vitro and injected into the patient to mark the tumor cells
for destruction. Other antibodies, aimed at the patient’s immune cells
rather than the cancer cells, can promote the elimination of cancer cells
by neutralizing the inhibitory cell-surface proteins that keep the killer
lymphocytes of the immune system (discussed in Chapter 18) in check.
Such “checkpoint inhibitor” antibodies, which unleash a killer cell attack
on cancer cells, are proving to be remarkably effective in the treatment of
certain cancers, such as melanomas, even after they have metastasized
(Figure 20−53).
In some cancers, the products of specific oncogenes can be targeted
directly so as to block their action, causing the cancer cells to die. In