Received 6/15/97 Accepted 6/28/97

Apoptosis research remains a field in full expansion with critical discoveries being reported almost weekly. However, despite the enormous progress which has been made so far, we still know relatively little about the regulation and intersection of the central pro- and anti-apoptotic pathways inside the cell. Although recent biochemical data suggest ways in which Bcl-2 family proteins interact with and modulate cysteine protease activity, the precise biochemical mechanisms for this modulation as well as the role of putative signaling intermediates like cytochrome C remain to be discovered. Continued study of these cell death signaling pathways will hopefully provide a wealth of new targets for apoptosis-inducing therapies in the clinics. Finding cell death triggers which work independently of p53 may enhance the development of antineoplastic therapies. In addition, the study of p53 positive tumors which are resistant to apoptosis may assist in identifying additional death modulators downstream of p53. Understanding which oncogenically-induced apoptotic activities remain in tumor cells could further advance our ability to trigger apoptosis in a transformation-selective manner.