Signal transduction pathways: the molecular basis for targeted therapies.

The elucidation of the signal transduction pathways that regulate cell growth and differentiation has led to a number of exciting opportunities for novel cancer therapies. It is now well known that growth factors and cell matrix molecules activate cognate growth factor receptors and integrins, respectively, to initiate a complex signaling cascade that ultimately targets the nucleus, cell surface, and mitochondria. Signaling to these target molecules results in the regulation of gene transcription, cell adhesion and motility, and cell survival, all of which are integral parts of cellular growth control mechanisms. As a result of increased understanding of cell growth regulation mechanisms, a number of novel therapeutic agents have been developed and tested in preclinical models and, to some extent, in clinical trials. Based on our current understanding of growth regulation in normal and cancer cells, one would predict that these new agents could influence proliferation and survival of cancer cells, as well as their response to traditional cytotoxic therapies. In this overview, the mechanistic basis for the use of signal transduction-targeted novel therapeutics is presented, along with predictions regarding how they may interact with ionizing radiation in different subgroups of patients. Copyright 2002, Elsevier Science (USA). All rights reserved.