ABSTRACT

Investigations into the causes of human cancer have increasingly focused on the molecular basis of its development. Although we now understand many facets of cellular transformation, the event(s) responsible for many of these changes still remain ill defined. Recent reports have delineated some important changes during malignant transformation, including aberrant growth factor signaling, defects in programmed cell death, altered interactions in the tumor microenvironment, and inappropriate differentiation patterns. Many of these changes can arise from altered proto-oncogene activity due to increased expression, mutations, or translocation. However, the loss or inactivation of specific genetic information, that is, tumor suppressor genes, during human neoplastic initiation and progression has also emerged as an equally potent mechanism for these changes. Indeed, without an understanding of these molecular events, the relative contributions of genetic susceptibility and environmental factors to the development of human cancer remain nebulous.