Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors

International Journal of Molecular Sciences

Xiaonan Zhang³  Angelo de Milito²  Maria Hägg Olofsson²  Joachim Gullbo¹  Padraig D’Arcy³  Stig Linder³ 

[1] Department of Immunology, Genetics and Pathology, Section of Oncology, Uppsala University, 751 85 Uppsala, Sweden;Department of Oncology-Pathology, Karolinska Institute, SE-171 76 Stockholm, Sweden;Department of Medical and Health Sciences, Linköping University, SE-581 83 Linköping, Sweden;

关键词: cancer therapy;    solid tumor;    mitochondria;    oxidative phosphorylation;    glucose;    multicellular tumor spheroids;   

DOI  :  10.3390/ijms161126020

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.