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Targeting tumor cell metabolism with statins

Oncogene volume 31, pages 4967–4978 (2012)Cite this article

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Abstract

The mevalonate pathway is a core biochemical process, crucial for the generation of cholesterol and other key metabolic end products. The rate-limiting enzyme of the mevalonate pathway, hydroxymethylglutaryl coenzyme A reductase (HMGCR), is safely and effectively targeted by the statin family of inhibitors to treat hypercholesterolemia. The anticancer activity of statins has also been widely reported, yet the tumor-selective mechanisms that mediate these antiproliferative effects remain largely unclear. The importance of altered metabolism in the context of tumorigenesis has received renewed attention as metabolic changes entwined with the molecular hallmarks of cancer have been elucidated. Although several metabolic pathways have been linked to cancer progression and etiology, it was only recently that HMGCR and the mevalonate pathway were also shown to have a distinct role in cellular transformation. In this review, we chart the historical progression of statins from cholesterol-lowering blockbusters to anticancer agents with imminent potential, and further discuss an emerging role for HMGCR and the mevalonate pathway in the metabolic reprogramming of cancer.

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Acknowledgements

We gratefully thank members of the Penn lab for helpful discussions and critical review of the manuscript. Financial support: This work was undertaken, in part, thanks to funding from the Canada Research Chairs Program (L.Z.P), the Ontario Institute for Cancer Research through funding provided by the Province of Ontario (L.Z.P.), the Canadian Breast Cancer Foundation, Ontario Region (L.Z.P.), the Excellence In Radiation Research for the 21st Century Strategic Training Initiative In Health Research from the Canadian Institutes for Health Research (J.W.C.), and the Ontario Ministry of Health and Long Term Care. The views expressed do not necessarily reflect those of the Ontario Ministry of Health and Long Term Care.

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    J W Clendening & L Z Penn

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Clendening, J., Penn, L. Targeting tumor cell metabolism with statins. Oncogene 31, 4967–4978 (2012). https://doi.org/10.1038/onc.2012.6

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