The reverse Warburg effect is likely to be an Achilles' heel of cancer that can be exploited for cancer therapy

Abstract

// Yaojie Fu 1, 2, 3 , Shanshan Liu 1, 2, 3 , Shanghelin Yin 1, 2, 3 , Weihong Niu 1, 2 , Wei Xiong 1, 2 , Ming Tan 4 , Guiyuan Li 1, 2 and Ming Zhou 1, 2 1 The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P. R. China 2 Cancer Research Institute, Central South University, Changsha, Hunan 410078, P. R. China 3 Medical School of Xiangya, Central South University, Changsha, Hunan 410013, P. R. China 4 Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA Correspondence to: Ming Zhou, email: zhouming2001@163.com Keywords: the Warburg effect, the reverse Warburg effect, cancer glucose metabolism, lactate shuttle, oxidative stress Received: March 03, 2017 Accepted: April 25, 2017 Published: May 25, 2017 ABSTRACT Although survival outcomes of cancer patients have been improved dramatically via conventional chemotherapy and targeted therapy over the last decades, there are still some tough clinical challenges that badly needs to be overcome, such as anticancer drug resistance, inevitable recurrences, cancer progression and metastasis. Simultaneously, accumulated evidence demonstrates that aberrant glucose metabolism termed ‘the Warburg effect’ in cancer cell is closely associated with malignant phenotypes. In 2009, a novel ‘two-compartment metabolic coupling’ model, also named ‘the reverse Warburg effect’, was proposed and attracted lots of attention. Based on this new model, we consider whether this new viewpoint can be exploited for improving the existent anti-cancer therapeutic strategies. Our review focuses on the paradigm shift from ‘the Warburg effect’ to ‘the reverse Warburg effect’, the features and molecular mechanisms of ‘the reverse Warburg effect’, and then we discuss its significance in fundamental researches and clinical practice.