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About one in five of us will die of cancer, but that is not why we devote a chapter to this disease. Cancer cells break the most basic rules of cell behavior by which multicellular organisms are built and maintained, and they exploit every kind of opportunity to do so. These transgressions help to reveal what the normal rules are and how they are enforced. As a result, cancer research helps to illuminate the fundamentals of cell biology—especially cell signaling (Chapter 15), the cell cycle and cell growth (Chapter 17), programmed cell death (apoptosis, Chapter 18), and the control of tissue architecture (Chapters 19 and 22). Of course, with a deeper understanding of these normal processes, we also gain a deeper understanding of the disease and better tools to treat it.
In this chapter, we first consider what cancer is and describe the natural history of the disease from a cellular standpoint. We then discuss the molecular changes that make a cell cancerous. And we end the chapter by considering how our enhanced understanding of the molecular basis of cancer is leading to improved methods for its prevention and treatment.
The body of an animal operates as a society or ecosystem, whose individual members are cells that reproduce by cell division and organize themselves into collaborative assemblies called tissues. This ecosystem is very peculiar, however, because self-sacrifice—as opposed to survival of the fittest—is the rule. Ultimately, all of the somatic cell lineages in animals are committed to die: they leave no progeny and instead dedicate their existence to the support of the germ cells, which alone have a chance of continued survival (discussed in Chapter 21). There is no mystery in this, for the body is a clone derived from a fertilized egg, and the genome of the somatic cells is the same as that of the germ-cell lineage that gives rise to sperm or eggs. By their self-sacrifice for the sake of the germ cells, the somatic cells help to propagate copies of their own genes.
Thus, unlike free-living cells such as bacteria, which compete to survive, the cells of a multicellular organism are committed to collaboration. To coordinate their behavior, the cells send, receive, and interpret an elaborate set of extracellular signals that serve as social controls, directing cells how to act (discussed in Chapter 15). As a result, each cell behaves in a socially responsible manner—resting, growing, dividing, differentiating, or dying—as needed for the good of the organism.
Molecular disturbances that upset this harmony mean trouble for a multicellular society. In a human body with more than 1014 cells, billions of cells experience mutations every day, potentially disrupting the social controls. Most dangerously, a mutation may give one cell a selective advantage, allowing it to grow and divide slightly more vigorously and survive more readily than its neighbors and in this way to become a founder of a growing mutant clone. A mutation that promotes such selfish behavior by individual members of the cooperative can jeopardize the future of the whole enterprise. Over time, repeated rounds of mutation, competition, and natural selection operating within the population of somatic cells can cause matters to go from bad to worse. These are the basic ingredients of cancer: it is a disease in which an individual mutant clone of cells begins by
CANCER-CRITICAL GENES: hOW ThEY ARE FOUND AND WhAT ThEY DO