Clinical relevance of autophagic therapy in cancer: Investigating the current trends, challenges, and future prospects

Abstract

Oncophagy (cancer-related autophagy) has a complex dual character at different stages of tumor progression. It remains an important clinical problem to unravel the reasons that propel the shift in the role of oncophagy from tumor inhibition to a protective mechanism that shields full-blown malignancy. Most treatment strategies emphasize curbing protective oncophagy while triggering the oncophagy that is lethal to tumor cells. In this review, we focus on the trends in current therapeutics as well as various challenges in clinical trials to address the oncophagic dilemma and evaluate the potential of these developing therapies. A detailed analysis of the clinical and pre-clinical scenario of the anticancer medicines highlights the various inducers and inhibitors of autophagy. The ways in which tumor stage, the microenvironment and combination drug treatment continue to play an important tactical role are discussed. Moreover, autophagy targets also play a crucial role in developing the best possible solution to this oncophagy paradox. In this review, we provide a comprehensive update on the current clinical impact of autophagy-based cancer therapeutic drugs and try to lessen the gap between translational medicine and clinical science.

• Autophagy
• apoptosis
• cancer patients
• drugs
• therapy
• oncophagy
• clinical trials
• translational medicine

Acknowledgements

We thank the National Institute of Technology, Rourkela, for providing a facility for this work. We acknowledge Mr. Deependra Kumar Ban, Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, for fruitful discussion and constructive suggestions. We are highly thankful to Miss. Anuttoma Ray, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, USA, who generously helped us to prepare the final revised form of the manuscript.

Declaration of interest

Research support was partly provided by the Rapid Grant for Young Investigators (RGYI) Award [Grant Number: BT/PR1/5090/GBD/27/309/2011], the Department of Biotechnology [Grant Number: BT/PR7791/BRB/10/1187/2013]; the Science and Engineering Research Board (SERB), the Department of Science and Technology [Grant Number: SR/SO/BB-0101/2012]; the Council of Scientific and Industrial Research (CSIR) [Grant Number: 37(1608)/13/EMR-II] Human Resource Development Group, Government of India. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. We apologize to researchers whose studies on autophagy we were unable to cite due to the length of this review.

Supplementary material available online