It has become clear that tumors arise from excessive cell proliferation and a corresponding
reduction in cell death. Tumors result from the successive accumulation of
mutations in key regulatory target genes over time. During the 1980s, a number of
oncogenes were characterized, whereas from the 1990s to the present, the emphasis
shifted to tumor suppressor genes (TSGs). It has become clear that oncogenes and
tumor suppressor genes function in the same pathways, providing positive and negative
growth regulatory activities. The signaling pathways controlled by these genes
involve virtually every process in cell biology, including nuclear events, cell cycle,
cell death, cytoskeletal, cell membrane, angiogenesis, and cell adhesion effects. Tumor
suppressor genes are mutated in hereditary cancer syndromes, as well as somatically in
nonhereditary cancers. In their normal state, TSGs control cancer development and progression,
as well as contribute to the sensitivity of cancers to a variety of therapeutics.
Understanding the classes of TSGs, the biochemical pathways they function in, and how
they are regulated provides an essential lesson in cancer biology. We cannot hope to
advance our current knowledge and to develop new and more effective therapies without
understanding the relevant pathways and how they influence the present approaches to
therapy. Moreover, it is important to be able to access the powerful tools now available
to discover these genes, as well as their links to cell biology and growth control.