SURVIVAL FACTORS, INTRACELLULAR SIGNAL-TRANSDUCTION, AND THE ACTIVATION OF ENDONUCLEASES IN APOPTOSIS

Cell survival is normally mediated by factors in the extracellular env ironment whereas genetic changes that constitutively activate intracel lular survival pathways often occur in cancer It is suggested that a R as/Raf/MAP kinase-dependent pathway is critical for cell survival Apop tosis results from loss of these survival factors or deregulation of s urvival pathways. If protein kinase cascades mediate survival, then it is likely that phosphatases mediate apoptosis. Potential targets for dephosphorylation include regulators of ion homeostasis as these have been implicated in the regulation of endonucleases associated with apo ptosis. Survival factors also modulate anticancer drug response and un derstanding these pathways may improve therapy.