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Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors
Linkoping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.;Karolinska Inst, Dept Oncol Pathol, SE-17176 Stockholm, Sweden..
Karolinska Inst, Dept Oncol Pathol, SE-17176 Stockholm, Sweden..
Karolinska Inst, Dept Oncol Pathol, SE-17176 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
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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) Published
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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
2015. Vol. 16, no 11, 27313-27326 p.
Keyword [en]
cancer therapy, solid tumor, mitochondria, oxidative phosphorylation, glucose, multicellular tumor spheroids
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-276939DOI: 10.3390/ijms161126020ISI: 000365648300090PubMedID: 26580606OAI: oai:DiVA.org:uu-276939DiVA: diva2:905634
Funder
Swedish Research CouncilSwedish Cancer SocietySwedish Childhood Cancer Foundation
Available from: 2016-02-23 Created: 2016-02-16 Last updated: 2017-11-30Bibliographically approved

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Gullbo, Joachim

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