Emerging strategies to effectively target autophagy in cancer

Abstract

Autophagy serves a dichotomous role in cancer and recent advances have helped delineate the appropriate settings where inhibiting or promoting autophagy may confer therapeutic efficacy in patients. Our evolving understanding of the molecular machinery responsible for the tightly controlled regulation of this homeostatic mechanism has begun to bear fruit in the way of autophagy-oriented clinical trials and promising lead compounds to modulate autophagy for therapeutic benefit. In this manuscript we review the recent preclinical and clinical therapeutic strategies that involve autophagy modulation in cancer.

Figure 1

Autophagy regulators and points of intervention. (a) Autophagy occurs through a multistep process that includes four control points: initiation, nucleation, maturation, and lysosomal fusion and degradation of autophagosome contents. Successful autophagy results in the recycling of nutrients into the cytoplasm. (b–e) Autophagy is regulated on multiple levels with four major classes of regulation including posttranslational, transcriptional, epigenetic and metabolic regulation. Potential druggable targets are depicted (red star) with a promise to better modulate autophagy than strategies currently being implored.