Cancer metabolism: key players in metabolic reprogramming

Over 80 years ago, Warburg discovered that cancer cells generate ATP through the glycolytic pathway, even in the presence of oxygen. The finding of this phenomenon, termed the "Warburg effect," stimulated much research on tumorigenesis, but few explanations were forthcoming to explain the observation. Recently, advanced developments in molecular biology and high-throughput molecular analyses have revealed that many of the signaling pathways altered by gene mutations regulate cell metabolism in cancer. Furthermore, mutations in isocitrate dehydrogenase 1 and 2 were shown to elevate 2-hydroxyglutarate, which led to changes in α-ketoglutarate-dependent dioxygenase enzyme activity, resulting in an increased risk of malignant tumors. Although these findings led to a renewed interest in cancer metabolism, our knowledge on the specifics of tumor metabolism is still fragmented. This paper reviews recent findings related to key transcription factors and enzymes that play an important role in the regulation of cancer metabolism.