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Apoptosis


 Avi Ashkenazi and Vishva Dixit

Staff Scientists Avi Ashkenazi and Vishva Dixit work to fight cancer by harnessing the biological mechanism of apoptosis, or programmed cell death.
Apoptosis is the mechanism by which cells self-destruct. This natural regulatory program for suicide exists in all cells, including cancer cells, and may prove extremely valuable in fighting the disease. Under normal conditions, apoptosis serves to eliminate damaged or unneeded cells from the organism. However, in cancer cells, this self-regulation program is silenced, allowing tumors to survive and grow.

Genentech researchers Vishva Dixit and Avi Ashkenazi are leading the discovery of new ways to activate the apoptosis machinery in cancer cells as a means of attacking tumors. One such gene, discovered by the Ashkenazi lab and independently at Immunex (now Amgen), encodes a protein called Apo2L/TRAIL, which triggers apoptosis in various types of cancer cells but not in most normal cells. Unlike conventional anti-cancer agents such as chemotherapy, Apo2L/TRAIL triggers apoptosis independently of the p53 tumor suppressor gene. Since more than half of human cancers acquire inactivating mutations in p53 that are associated with resistance to chemotherapy, Apo2L/TRAIL and its apoptosis-signaling receptors may provide an alternative pathway to switching on apoptosis in tumors. Preclinical studies demonstrate promising apoptosis-based anti-tumor activity of Apo2L/TRAIL and a strong cooperation between this biologic agent and chemotherapy. Apo2L/TRAIL is jointly being prepared by Genentech and Amgen for human clinical trials.

Director and staff scientist Avi Ashkenazi along with Vishva Dixit, vice president of Molecular Oncology, work to fight cancer by harnessing the biological mechanism of apoptosis, or programmed cell death.