Mitochondrial and postmitochondrial survival signaling in cancer

Cancer cells are resistant to conventional chemotherapy and radiotherapy, however, the molecular mechanisms of resistance to therapy remain unclear. Cellular survival machinery protects mitochondrial integrity against endogenous or exogenous stresses. Prodeath molecules orchestrate around mitochondria to initiate and execute cell death in cancer, and also play an underappreciated role in survival of cancer cells. Prosurvival mechanisms can operate at mitochondrial and postmitochondrial levels to attenuate core apoptotic death program. It is intriguing to explore how prosurvival and prodeath molecules crosstalk to regulate mitochondrial functions leading to increased cancer cell survival. This review describes some putative survival mechanisms at mitochondria, which may play a role in designing effective agents for cancer prevention and therapy. These survival pathways may also have significance in understanding other human pathophysiological conditions including diabetes, cardiovascular, autoimmune, and neurodegenerative diseases.