Oncogenes and Tumor Suppressor Genes in Human Malignancies

This volume begins by reviewing selected malignancies in which the search for clinically relevant oncogenes has led to more focused studies on gain-of-function and loss-of-function genetic abnormalities, as well as autocrine and paracrine growth factor loops known to regulate tumor physiology and malignant cell behavior. Many of these genetic and functional abnormalities are shared by several different tumor types and are not uniformly present in all tumors of the same type. This observation brings up molecular questions about the tissue-specific determinants that underlie individual cancers and also gives added impetus to the suggestion that molecular abnormalities (referred to as tumor markers) be included among the histopathologic features used for clinical diagnosis and management. The remainder of the volume updates molecular mechanisms relating to select growth factor systems, oncogenes, and tumor suppressor genes introduced earlier in the disease-oriented chapters. These reviews convey the increasing fascination that comes with a greater understanding of tumor physiology. They reveal, for instance, that tumor cells can induce the secretion of paracrine growth factors from non-malignant tissues, thus usurping normal genetic programs reserved for fetal development or wound healing such as those that provide neovascularization for a malignant tissue colony. The uncovering of these subverted intercellular mechanisms, as well as the constitutively stimulated intracellular signaling pathways associated with activated oncogenes and mutated tumor suppressor genes, provide researchers with many new targets for the development of more specific and less toxic anticancer agents. A number of these novel gents are already in clinical test.