Apoptosis and a re-investigation of the biologic basis for cancer therapy.

Antitumor therapy has expanded beyond the previous notions of cytotoxic or biologic therapy to now include agents that induce differentiation (e.g. all trans-retinoic acid for induction of complete remission in patients with acute promyelocytic leukemia [23]) or apoptosis [91]. In fact, the phenomenon of apoptosis may be fundamental to the current understanding of carcinogenesis [11] and may also underlie the effectiveness of some forms of chemotherapy [4,5,18,39,56,59,67], radiation therapy [19,44,52,60,64, 77,78,85] and the interferons [73]. The process of apoptosis has been shown to be responsible for the normal elimination of cells with damaged DNA [81] as well as other potentially dangerous cells such as autoreactive T-lymphocytes [14]. Therefore, although much attention has been given to oncogenes that induce cellular proliferation, one can easily see how the same result (i.e. neoplasia) could be obtained when the ability of a cell to undergo apoptosis is lost.