ABSTRACT
Since the discovery of the c-src oncogene it has been clear that molecular changes involving oncogenes and tumor suppressor genes are critical in tumorigenesis. It has been hypothesized that, at a minimum, 3-8 mutational events are needed to disrupt critical cellular pathways and lead to malignant transformation. Steps felt to be critical to oncogenesis include an increase in growth signals, loss of tumor suppressors, disruption of apoptotic pathways, limitless cell divisions from telomerase reactivation, and altered DNA repair mechanisms. Even then, tumor cells can only form 1-2 mm nodules before being limited by diffusion for oxygen, nutrients, growth factors, and elimination of waste. At this point, further
growth requires angiogenesis, the ability to stimulate a new vasculature. In addition, metastatic potential requires the ability to penetrate the basement membrane, grow independent of adhesion, and invade host tissues. Molecular alterations detected in each of these steps contribute to various stages of tumor development and thus offer potential molecular therapeutic targets (1).
