Survival factors, intracellular signal transduction, and the activation of endonucleases in apoptosis.

Cell survival is normally mediated by factors in the extracellular environment, whereas genetic changes that constitutively activate intracellular survival pathways often occur in cancer. It is suggested that a Ras/Raf/MAP kinase-dependent pathway is critical for cell survival. Apoptosis results from loss of these survival factors or deregulation of survival 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 apoptosis. Survival factors also modulate anticancer drug response and understanding these pathways may improve therapy.