Genetics and new approaches to cancer therapy.

Abstract

The past two decades have been golden years for the genetics of cancer. It has become clear through the work of countless laboratory groups that both inherited and sporadic cancers arise through defects or misregulations of their genomes. Several dozen dominantly acting oncogenes have been identified, shown to be deregulated in human tumors and to positively influence one or another aspect of tumor development or behavior in experimental systems. A smaller, but still substantial, number of recessively mutated tumor suppressor genes have also been identified which, in defective form, predispose to malignancy, both in people and in genetically manipulated rodent models. The cartography of the order, accumulation and interactions of genetic lesions during tumor initiation and progression has reasonable detail for many human tumor types. Such information is proving to be tremendously valuable in diagnosis and in grouping patients into prognostic categories. There is every reason to believe that the continued use of increasingly sophisticated genomic and proteomic technologies will add another order of magnitude to the precision of such conclusions.