Growth factor signaling in cell survival: Implications for cancer treatment

Cells of multicellular organisms require extracellular signals to survive. Numerous studies have implicated a variety of intracellular signaling pathw ays, including PI-3 kinase/Akt, Ras/mitogen-activated protein kinase, and J ak/signal transducers and activators of transcription, as effectors of thes e extracellular trophic factors. Binding of growth factors to their respect ive receptors results in the activation of individual and combined pathways resulting in pleiotropic effects on cellular biochemistry. Over the past d ecade, investigation of these pathways has provided insight into the mechan ism of cell survival and apoptosis itself. The results of these studies are providing new clues for therapeutic intervention in human disease. In this review, we focus on advances in our current understanding of the receptor signaling pathways that regulate apoptosis. Implications for the pharmacolo gical manipulation of apoptosis in the treatment of cancer are also discuss ed.