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Modulation of Mitochondrial Metabolic Reprogramming and Oxidative Stress to Overcome Chemoresistance in Cancer

1
CRG-Centre for Genomic Regulation, 08003 Barcelona, Spain
2
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
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Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, 7100 Foggia, Italy
4
Laboratory of Pre-Clinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 135; https://doi.org/10.3390/biom10010135
Received: 19 November 2019 / Revised: 18 December 2019 / Accepted: 7 January 2020 / Published: 14 January 2020
(This article belongs to the Special Issue Targeting Tumor Metabolism: From Mechanisms to Therapies)
Metabolic reprogramming, carried out by cancer cells to rapidly adapt to stress such as hypoxia and limited nutrient conditions, is an emerging concepts in tumor biology, and is now recognized as one of the hallmarks of cancer. In contrast with conventional views, based on the classical Warburg effect, these metabolic alterations require fully functional mitochondria and finely-tuned regulations of their activity. In turn, the reciprocal regulation of the metabolic adaptations of cancer cells and the microenvironment critically influence disease progression and response to therapy. This is also realized through the function of specific stress-adaptive proteins, which are able to relieve oxidative stress, inhibit apoptosis, and facilitate the switch between metabolic pathways. Among these, the molecular chaperone tumor necrosis factor receptor associated protein 1 (TRAP1), the most abundant heat shock protein 90 (HSP90) family member in mitochondria, is particularly relevant because of its role as an oncogene or a tumor suppressor, depending on the metabolic features of the specific tumor. This review highlights the interplay between metabolic reprogramming and cancer progression, and the role of mitochondrial activity and oxidative stress in this setting, examining the possibility of targeting pathways of energy metabolism as a therapeutic strategy to overcome drug resistance, with particular emphasis on natural compounds and inhibitors of mitochondrial HSP90s. View Full-Text
Keywords: cancer metabolic reprogramming; oxidative stress; drug resistance; tumor necrosis factor receptor associated protein 1 (TRAP1); heat shock protein 90 (HSP90); targeting metabolism for cancer therapy cancer metabolic reprogramming; oxidative stress; drug resistance; tumor necrosis factor receptor associated protein 1 (TRAP1); heat shock protein 90 (HSP90); targeting metabolism for cancer therapy
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Avolio, R.; Matassa, D.S.; Criscuolo, D.; Landriscina, M.; Esposito, F. Modulation of Mitochondrial Metabolic Reprogramming and Oxidative Stress to Overcome Chemoresistance in Cancer. Biomolecules 2020, 10, 135.

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