Understanding Tumor Metabolism and its Potential as a Target for the Treatment of Cancer
- Pp. 151-190 (40)Ana Carolina Santos de Souza, Alexandre Donizeti Martins Cavagis, Carmen Veríssima Ferreira and Giselle Zenker Justo
The role played by oncogenes and tumor suppressors in the genesis of cancer is well established. Considering that cancer cells are a product of genetic disorders that alter crucial intracellular signaling pathways associated with the regulation of survival, proliferation, differentiation and death mechanisms it is not surprising that traditional antitumor approaches target specific molecular players whose action/expression is altered in cancer cells. However, because the physiology of normal cells is controlled by the same signaling pathways that are disturbed in cancer cells many cancer therapies also cause important side effects and multidrug resistance, the main causes of therapy failure. Since the pioneering work of Otto Warburg, over 80 years ago, the subversion of normal cellular metabolism by cancer cells has been highlighted by many studies. In recent years, the study of tumor metabolism has received considerable attention because metabolic transformation is now recognized as a crucial cancer hallmark and a direct consequence of disturbances in oncogenes and tumor suppressors. Far from being a completely understood phenomenon, metabolic transformation constitutes a challenge for researchers and a potential target for cancer therapies. In this chapter, we describe the anabolic and catabolic pathways of cancer cell metabolism, compare their functions and regulation with those of non-tumor cell metabolism and discuss some of the major questions in this field of investigation. We also discuss tumor metabolism and metabolic transformations from the perspective of oncogenes, tumor suppressors, miRNAs and protein signaling pathways. Finally, recent attempts to target metabolism as a treatment for cancer are discussed.