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The Role of Oxidative Metabolism in Tumorigenesis and Drug Resistance.

Authors :
Marcucci F
Rumio C
Source :
Discovery medicine [Discov Med] 2024 Jun; Vol. 36 (185), pp. 1109-1126.
Publication Year :
2024

Abstract

Aerobic glycolysis, i.e., non-oxidative glycolysis occurring under aerobic conditions (the so-called Warburg effect) is now recognized as a hallmark of cancer. However, evidence increasingly indicates that upregulated oxidative metabolism is also pivotal in tumorigenesis. In this article, we discuss factors that upregulate oxidative metabolism in tumor cells. These factors are associated with tumor cell-intrinsic and -extrinsic stimuli including antitumor drugs, requirements related to the different steps of tumorigenesis (initiation and acquisition of cancer stem-like cell functions, primary tumor growth, quiescence, metastatic dissemination), factors related to the phenotypic changes of tumor cells (e.g., autophagy and epithelial-mesenchymal transition), and particular metabolic requirements of proliferating tumor cells. In this context, we also discuss drug resistance associated with upregulated oxidative metabolism. We conclude by proposing a model whereby these factors, either individually or in combination, promote upregulation of oxidative metabolism. In the following, we address some mechanistic aspects that underlie the upregulation of oxidative metabolism and discuss the consequences on tumor prognosis. In the conclusion section of this article, we discuss possible therapeutic implications of the knowledge gathered in this field over the years.

Details

Language :
English
ISSN :
1944-7930
Volume :
36
Issue :
185
Database :
MEDLINE
Journal :
Discovery medicine
Publication Type :
Academic Journal
Accession number :
38926098
Full Text :
https://doi.org/10.24976/Discov.Med.202436185.102