The Emperor of All Maladies: A Biography of Cancer

by Siddhartha Mukherjee

By the late 1970s, Varmus, Bishop, and Knudson could begin to describe the core molecular aberration of the cancer cell, stitching together the coordinated actions of oncogenes and anti-oncogenes. Cancer genes, Knudson proposed, came in two flavors. “Positive” genes, such as src, are mutant activated versions of normal cellular genes. In normal cells, these genes accelerate cell division, but only when the cell receives an appropriate growth signal. In their mutant form, these genes are driven into perpetual hyperactivity, unleashing cell division beyond control. An activated proto-oncogene, to use Bishop’s analogy, is “a jammed accelerator” in a car. A cell with such a jammed accelerator careens down the path of cell division, unable to cease mitosis, dividing and dividing again relentlessly. “Negative” genes, such as Rb, suppress cell division. In normal cells, these anti-oncogenes, or tumor suppressor genes, provide the “brakes” to cellular proliferation, shutting down cell division when the cell receives appropriate signals. In cancer cells, these brakes have been inactivated by mutations. In cells with missing brakes, to use Bishop’s analogy again, the “stop” signals for mitosis can no longer be registered. Again, the cell divides and keeps dividing, defying all signals to stop.