Abstract

Cancer cells have evolved to develop sets of survival strategies to enable them not only to survive and ward off apoptosis-inducing effects of most chemotherapeutic drugs in current use but also proliferate and invade their surrounding healthy tissue. In the 1920’s, based on his pioneering research, Warburg hypothesized cancer cells rely on glycolysis for energy production to sustain their growth because their mitochondrial metabolism is dysfunctional. This review focuses on the current advances in cancer cell metabolism as a result of the recent resurgence of interests in the “Warburg hypothesis” (also called “Warburg effect”) and discusses how these advances have revealed potential anti-cancer drug targets. Additionally, we will also discuss metabolic pathways that are critically coupled to cancer cell survival and proliferation, thereby uncovering other putative anti-cancer drug targets for therapeutic consideration. Thus, we hope to provide a forward-looking framework for discussing and designing new anti-cancer therapies.

Keywords: Targeting tumor metabolism; Tumor cell metabolic phenotypes; Warburg hypothesis or Effect; Reverse Warburg Effect; and Multi-target approach; Anti-cancer drug discovery