Reversing cancer from inside and out: oncogene addiction, cellular senescence, and the angiogenic switch.

Cancer is largely caused by genetic events that result in the mutation of oncogenes or tumor suppressor genes, leading to cell autonomous proliferation and growth. The repair of these mutant gene products may be expected to subvert this neoplastic behavior. Indeed, oncogene inactivation can result in the elimination of all or almost all tumor cells by various mechanisms through the phenomena described as oncogene addiction. Recently, we have shown that oncogene addiction occurs through at least two broad classes of mechanisms: tumor cell intrinsic mechanisms of cellular senescence and apoptosis; and tumor cell extrinsic host-dependent mechanisms that include the shut-down of angiogenesis. We have argued that the abatement of oncogenic activity within a cancer cell not only leads to the demise of a tumor from within but also through the instruction of the restoration of the microenvironment.