Pro-survival autophagy and cancer cell resistance to therapy

Abstract

Resistance to therapy is one of the prime causes for treatment failure in cancer and recurrent disease. In recent years, autophagy has emerged as an important cell survival mechanism in response to different stress conditions that are associated with cancer treatment and aging. Autophagy is an evolutionary conserved catabolic process through which damaged cellular contents are degraded after uptake into autophagosomes that subsequently fuse with lysosomes for cargo degradation, thereby alleviating stress. In addition, autophagy serves to maintain cellular homeostasis by enriching nutrient pools. Although autophagy can act as a double-edged sword at the interface of cell survival and cell death, increasing evidence suggest that in the context of cancer therapy-induced stress responses, it predominantly functions as a cell survival mechanism. Here, we provide an up-to-date overview on our current knowledge of the role of pro-survival autophagy in cancer therapy at the preclinical and clinical stages and delineate the molecular mechanisms of autophagy regulation in response to therapy-related stress conditions. A better understanding of the interplay of cancer therapy and autophagy may allow to unveil new targets and avenues for an improved treatment of therapy-resistant tumors in the foreseeable future.

Keywords: Cancer; Pro-survival autophagy; Stress condition; Therapy resistance.