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The Roles of Therapy-Induced Autophagy and Necrosis in Cancer Treatment

Authors' Affiliation: Abramson Cancer Center at the University of Pennsylvania, Philadelphia, Pennsylvania

Requests for reprints: Craig B. Thompson, Abramson Cancer Center at the University of Pennsylvania, 450 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104. Phone: 215-746-5515; Fax: 215-746-5511; E-mail: craig{at}mail.med.upenn.edu.

Abstract

Metabolic and therapeutic stresses activate several signal transduction pathways that regulate cell death and cell survival in cancer cells. Although decades of research unraveled the pathways that regulate apoptosis and allowed the development of novel diagnostic and therapeutic modalities in cancer treatment, only recently has the regulation and significance of tumor cell autophagy and necrosis become the focus of investigations. Necrosis is an irreversible inflammatory form of cell death. In contrast, autophagy is a reversible process that can contribute both to tumor cell death and survival. This review describes recent advances in understanding the regulation of autophagy and necrosis and their implications for cancer therapy. Currently available methods to measure autophagy and necrosis are highlighted. The effect of tumor cell autophagy and necrosis on host immunity is explored. Finally, therapeutic approaches that target autophagy and necrosis in cancer are described.

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