Defining the Molecular Basis of Tumor Metabolism: a Continuing Challenge Since Warburg's Discovery

Author(s)

Santos de Souza, Ana Carolina ^[1] ; Justo, Giselle Zenker ^{[2, 3]} ; de Araujo, Daniele Ribeiro ^[1] ; Martins Cavagis, Alexandre D. ^[4]

Affiliation

^[1] Univ Fed ABC UFABC, CCNH, Santo Andre - Brazil

^[2] Univ Fed Sao Paulo UNIFESP, Dept Bioquim, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo UNIFESP, Dept Ciencias Biol, Sao Paulo - Brazil

^[4] Univ Fed Sao Carlos UFSCar, DFQM, Sorocaba - Brazil

• Document type: Review article
• Source: CELLULAR PHYSIOLOGY AND BIOCHEMISTRY; v. 28, n. 5, p. 771-792, 2011.
• Web of Science Citations: 15

Abstract

Cancer cells are the product of genetic disorders that alter crucial intracellular signaling pathways associated with the regulation of cell survival, proliferation, differentiation and death mechanisms. The role of oncogene activation and tumor suppressor inhibition in the onset of cancer is well established. Traditional antitumor therapies target specific molecules, the action/expression of which is altered in cancer cells. However, since the physiology of normal cells involves the same signaling pathways that are disturbed in cancer cells, targeted therapies have to deal with 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 metabolism displayed by cancer cells has been highlighted by many studies. Recently, the study of tumor metabolism has received much attention because metabolic transformation is a crucial cancer hallmark and a direct consequence of disturbances in the activities of oncogenes and tumor suppressors. In this review we discuss tumor metabolism from the molecular perspective of oncogenes, tumor suppressors and protein signaling pathways relevant to metabolic transformation and tumorigenesis. We also identify the principal unanswered questions surrounding this issue and the attempts to relate these to their potential for future cancer treatment. As will be made clear, tumor metabolism is still only partly understood and the metabolic aspects of transformation constitute a major challenge for science. Nevertheless, cancer metabolism can be exploited to devise novel avenues for the rational treatment of this disease. Copyright (C) 2011 S. Karger AG, Basel (AU)

• FAPESP's process: 10/16050-9 - Exploring the multifactorial side of multidrug resistance (MDR)event in tumoral cells: evaluation of the roles performed by protein tyrposine phosphatases and energetic metabolism alterations
• Grantee: Ana Carolina Santos de Souza Galvão
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/11475-1 - Development and pharmacological evaluation of drug-delivery systems containing tramadol in thermoreversible hydrogels for pain treatment
• Grantee: Daniele Ribeiro de Araujo
• Support Opportunities: Regular Research Grants