The Warburg Effect and Beyond: Metabolic Dependencies for Cancer Cells

Abstract Current definitions of cancer are best realized as a list of traits or hallmarks, such as tissue invasion, metastasis, cell-autonomous growth, and resistance to apoptosis. A recent update included deregulated cellular energetics as an emerging hallmark. However, debate about tumor cell metabolism occupied center stage in the pre-oncogene era. Over the last 15 years, direct links of oncogenes and tumor suppressor genes to cell metabolism have brought cancer metabolism to the forefront once again. Current tools provide much greater opportunities for probing metabolic differences between normal and cancer cells, in some cases revealing flux through unexpected metabolic pathways. Metabolic networks may also be truncated, presenting opportunities for selective growth inhibition or death by targeting non-redundant pathways in cancer cells. These “metabolic dependencies” are not likely to be associated with classically defined oncogenes or computationally derived drivers and thus may require novel strategies for discovery.