Signalling Pathways as Targets in Cancer Prevention

Abstract

Normal cells constantly receive signals from their external and internal environments which determine whether they proliferate, differentiate, arrest cell growth, or undergo apoptosis. Transformed cells either fail to respond or receive inappropriate signals which favor proliferation and avoidance of apoptosis. Thus, it is no coincidence that many oncogenes and tumor suppressor genes are components of signalling pathways. Despite the great variety of cancer cell genotypes, it has been suggested that transformation is a result of a few essential changes in cell physiology which collectively dictate malignant phenotype. These acquired characteristics are self-sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis (Hanahan and Weinberg 2000). There are now examples, at least from in vitro studies, of chemopreventive agents which influence each of these acquired characteristics, suggesting the possibility of intervention at many stages of the carcinogenic process. As our understanding of the cell circuitry involved increases (Hanahan and Weinberg 2000), exciting new opportunities to target deregulated signalling pathways present themselves.