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Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
Uppsala University, Sweden.
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2015 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 16, no 11, 27313-27326 p.Article, review/survey (Refereed) PublishedText
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI AG , 2015. Vol. 16, no 11, 27313-27326 p.
Keyword [en]
cancer therapy; solid tumor; mitochondria; oxidative phosphorylation; glucose; multicellular tumor spheroids
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-123821DOI: 10.3390/ijms161126020ISI: 000365648300090PubMedID: 26580606OAI: diva2:892887

Funding Agencies|Vetenskapsradet; Cancerfonden; Radiumhemmets forskningsfonder; Barncancerfonden

Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2016-02-04

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Zhang, XiaonanD´arcy, PadraigLinder, Stig
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