Autophagy as a target for cancer therapy: new developments

utophagy as a target for cancer therapy: new developments Review (2908) Total Article Views Authors: Carew JS, Kelly KR, Nawrocki ST Published Date October 2012 Volume 2012:4 Pages 357 - 365 DOI: http://dx.doi.org/10.2147/CMAR.S26133 Received: 17 July 2012 Accepted: 09 September 2012 Published: 11 October 2012 Jennifer S Carew, Kevin R Kelly, Steffan T Nawrocki The Department of Medicine and Institute for Drug Development, Cancer Therapy and Research Center at The University of Texas Health Science Center, San Antonio, TX, USA Abstract: Autophagy is an evolutionarily conserved lysosomal degradation pathway that eliminates cytosolic proteins, macromolecules, organelles, and protein aggregates. Activation of autophagy may function as a tumor suppressor by degrading defective organelles and other cellular components. However, this pathway may also be exploited by cancer cells to generate nutrients and energy during periods of starvation, hypoxia, and stress induced by chemotherapy. Therefore, induction of autophagy has emerged as a drug resistance mechanism that promotes cancer cell survival via self-digestion. Numerous preclinical studies have demonstrated that inhibition of autophagy enhances the activity of a broad array of anticancer agents. Thus, targeting autophagy may be a global anticancer strategy that may improve the efficacy of many standard of care agents. These results have led to multiple clinical trials to evaluate autophagy inhibition in combination with conventional chemotherapy. In this review, we summarize the anticancer agents that have been reported to modulate autophagy and discuss new developments in autophagy inhibition as an anticancer strategy.