Apoptosis and Cancer

Cancer is a disease involving the abnormal accumulation of cells resulting from an imbalance of proliferation and programmed cell death. This review focuses on the mitochondrial apoptotic pathway, a mechanism of programmed cell death with particular relevance to cancer. Starting over 30 years ago, basic findings in model organisms have been combined with findings in clinical cytogenetics to uncover a family of proteins, the BCL-2 family, that regulates the commitment to apoptosis by controlling permeabilization of the mitochondrial outer membrane. Cancer cells are generally more poised to engage the apoptotic machinery than normal cells are, a fact that likely underlies much of the therapeutic index exploited by many types of cancer chemotherapy. More recently, small molecules directly targeting the antiapoptotic proteins of the BCL-2 family have entered the clinic for testing in cancer. One therapeutic, venetoclax (ABT-199), has recently gained FDA approval in a landmark achievement for the apoptosis community. Important future efforts will be directed at building combinations of agents that selectively induce apoptosis in cancer cells.