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Int. J. Mol. Sci. 2015, 16(11), 27313-27326; doi:10.3390/ijms161126020

Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors

1
Department of Medical and Health Sciences, Linköping University, SE-581 83 Linköping, Sweden
2
Department of Oncology-Pathology, Karolinska Institute, SE-171 76 Stockholm, Sweden
3
Department of Immunology, Genetics and Pathology, Section of Oncology, Uppsala University, 751 85 Uppsala, Sweden
*
Authors to whom correspondence should be addressed.
Academic Editor: Gopinadhan Paliyath
Received: 4 September 2015 / Revised: 20 October 2015 / Accepted: 2 November 2015 / Published: 13 November 2015
(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)
View Full-Text   |   Download PDF [1062 KB, uploaded 16 November 2015]   |  

Abstract

The disorganized nature of tumor vasculature results in the generation of microenvironments characterized by nutrient starvation, hypoxia and accumulation of acidic metabolites. Tumor cell populations in such areas are often slowly proliferating and thus refractory to chemotherapeutical drugs that are dependent on an active cell cycle. There is an urgent need for alternative therapeutic interventions that circumvent growth dependency. The screening of drug libraries using multicellular tumor spheroids (MCTS) or glucose-starved tumor cells has led to the identification of several compounds with promising therapeutic potential and that display activity on quiescent tumor cells. Interestingly, a common theme of these drug screens is the recurrent identification of agents that affect mitochondrial function. Such data suggest that, contrary to the classical Warburg view, tumor cells in nutritionally-compromised microenvironments are dependent on mitochondrial function for energy metabolism and survival. These findings suggest that mitochondria may represent an “Achilles heel” for the survival of slowly-proliferating tumor cells and suggest strategies for the development of therapy to target these cell populations. View Full-Text
Keywords: cancer therapy; solid tumor; mitochondria; oxidative phosphorylation; glucose; multicellular tumor spheroids cancer therapy; solid tumor; mitochondria; oxidative phosphorylation; glucose; multicellular tumor spheroids
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhang, X.; de Milito, A.; Olofsson, M.H.; Gullbo, J.; D’Arcy, P.; Linder, S. Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors. Int. J. Mol. Sci. 2015, 16, 27313-27326.

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