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Targeting cancer metabolism through synthetic lethality-based combinatorial treatment strategies

Bajpai, Richa; Shanmugam, Mala

doi: 10.1097/CCO.0000000000000467
INNOVATIVE AGENTS AND TREATMENT MODALITIES: Edited by Ahmad Awada and Steven T. Rosen

Purpose of review Targeting cancer metabolism for therapy has received much attention over the last decade with various small molecule inhibitors entering clinical trials. The present review highlights the latest strategies to target glucose and glutamine metabolism for cancer therapy with a particular emphasis on novel combinatorial treatment approaches.

Recent findings Inhibitors of glucose, lactate, and glutamine transport and the ensuing metabolism are in preclinical to clinical trial stages of investigation. Recent advances in our understanding of cell-intrinsic and cell-extrinsic factors that dictate dependence on these targets have informed the development of rational, synthetic lethality-based strategies to exploit these metabolic vulnerabilities.

Summary Cancer cells exhibit a number of metabolic alterations with functional consequences beyond that of sustaining cellular energetics and biosynthesis. Elucidating context-specific metabolic dependencies and their connections to oncogenic signaling and epigenetic programs in tumor cells represents a promising approach to identify new metabolic drug targets for cancer therapy.

Department of Hematology and Medical Oncology, Winship Cancer Institute, School of Medicine, Emory University, Atlanta, Georgia, USA

Correspondence to Mala Shanmugam, PhD, Winship Cancer Institute, School of Medicine, Emory University, 1365C Clifton Rd. NE, Suite C4002, Atlanta, GA 30322, USA. Tel: +1 404 727 3005; fax: +1 404 778 4755; e-mail: mala.shan@emory.edu

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