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Multicellularity has its advantages, but they come at a price. The division of labor in a complex organism means that every cell must perform its job and only its job, so an elaborate regulatory system evolved to keep cells in line. Nearly every one of the trillion or so cells in the human body, for instance, contains a full copy of the genome – the complete instruction set for building and maintaining a human being. Tight controls on which genes are activated, and when, inside any given cell determine that cell’s behavior and identity. A healthy skin cell executes only the genetic commands needed to fulfill its role in the skin. It respects neighbor-ing cells’ boundaries and cues, and when the regulatory systempermits, it divides to generate just enough new cells to repair a wound, never more.
Greek physician Hippocrates first used the term karkinos, or “crab,” in the fourth century B.C. to describe malignant tumors because their tendril-like projections into surrounding tissue reminded him of the arms of the crustacean. In Latin, the word for crab was cancer, and by the second century B.C. the great Roman physician Galen knew those spiny arms were just one sign that normal body tissues had gone out of control. He attributed the dysfunction to an excess of black bile. Modern scientists see a breakdown of the cellular regulatory system in the hallmarks of cancer: runaway growth, invasion of neighboring tissue and metastasis to far-off parts of the body.
The proteins and nucleic acids that control gene activity are themselves encoded by genes, so cancers begin with mutations that either disable key genes or, conversely, cause them to be overactive. Those changes initiate a cascade of imbalances that knock out downstream regulatory processes, and soon the cell is careening toward malignancy. So far efforts to identify the exact combination of mutations necessary to ignite a particular type of cancer—in the brain, the breast or elsewhere—have not yielded clear patterns. Once regulatory networks are destabilized, they can break down in ways as complex and diverse as the molecular pathways they regulate, making the precise origin of each instance of cancer unique. For all their internal chaos, though, cancer cells share some characteristics with stem cells—those primal body-building cells that are exempt from many constraints on normal cells. One important difference is that in stem cells, the full potential of the genome is controlled; in cancer, it is unleashed.