The Emperor of All Maladies: A Biography of Cancer

by Siddhartha Mukherjee

First, cancer cells are driven to grow because of the accumulation of mutations in their DNA. These mutations activate internal proto-oncogenes and inactivate tumor suppressor genes, thus unleashing the “accelerators” and “brakes” that operate during normal cell division. Targeting these hyperactive genes, while sparing their modulated normal precursors, might be a novel means to attack cancer cells more discriminately. Second, proto-oncogenes and tumor suppressor genes typically lie at the hubs of cellular signaling pathways. Cancer cells divide and grow because they are driven by hyperactive or inactive signals in these critical pathways. These pathways exist in normal cells but are tightly regulated. The potential dependence of a cancer cell on such permanently activated pathways is a second potential vulnerability of a cancer cell. Third, the relentless cycle of mutation, selection, and survival creates a cancer cell that has acquired several additional properties besides uncontrolled growth. These include the capacity to resist death signals, to metastasize throughout the body, and to incite the growth of blood vessels. These “hallmarks of cancer” are not invented by the cancer cell; they are typically derived from the corruption of similar processes that occur in the normal physiology of the body. The acquired dependence of a cancer cell on these processes is a third potential vulnerability of cancer.