The better we understand the tricks that cancer cells use to survive, proliferate, and spread, the better are our chances of finding ways to defeat them. The task is made more challenging because cancer cells are highly mutable and, like weeds or parasites, rapidly evolve resistance to treatments used to exterminate them.
Moreover, because mutations arise randomly, every case of cancer is likely to have its own unique combination of genes mutated. Even within an individual patient, tumor cells do not all contain the same genetic lesions. Thus, no single treatment is likely to work in every patient, or even for every cancer cell within the same patient. And the fact that cancers generally are not detected until the primary tumor has reached a diameter of 1 cm or more – by which time it consists of hundreds of millions of cells that are already genetically diverse and often have already begun to metastasize – makes treatment ever harder still.
Yet, in spite of these difficulties, an increasing number of cancers can be 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 simply cutting it out. Where surgery fails, therapies based on the intrinsic peculiarities of cancer cells can be used.
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 does of radiotherapy or DNA-damaging chemotherapy that leave normal cells relatively unharmed.
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 protein (Brca1 or Brca2) needed for accurate repair of double-strand breaks in DNA; the cancer cells survive by relying on alternative types of DNA repair mechanisms. Drugs that inhibit one of these alternative DNA repair mechanisms kill 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 have an intact double-strand break repair mechanisms, are relatively unaffected, and the drugs seem to have few side effects.
Another set of strategy aims to use the immune systems to kill the tumor cells, taking advantage of tumor-specific cell-surface molecules to target the attack. Antibodies that recognize these tumor molecules can be produced in vitro and injected into the patient to mark the tumor cells for destruction. Other antibodies, aimed to the immune cells, can promote the elimination of cancer cells by neutralizing the inhibitory cell-surface molecules that keep immune system’s killer cells in check. The latter antibodies have been remarkably effective in clinical trials and, in principle, should be useful for treating a variety of different cancers.
Retype from Essential Cell Biology 4th Ed. Page 720-721
Genome 4 