Cholesterol and Radiosensitivity
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Although there is some evidence in animal studies that cholesterol signaling mediates radiation sensitivity of normal tissues, until recently, no connection had been made between cholesterol signaling and tumor radiosensitivity. Aberrant cholesterol signaling in breast cancer promotes oncogenesis and tumor progression by either altering membrane fluidity, membrane associated rafts, or as a direct activator of transcription. Cholesterol is synthesized de novo by the mevalonate pathway. A causal role for hydroxy-3-methylglutaryl-coenzyme A reductase, a rate-limiting enzyme of the mevalonate pathway, in oncogenic transformation, progression, and sensitivity to treatment offers an opportunity for drugs that inhibit this enzyme (i.e., statins) as well as other cholesterol mediating strategies as radiosensitizing treatments. This review discusses potential mechanisms by which statins alter cholesterol signaling in breast cancer and potentially enhances radiation sensitivity and outcome with a special focus on inflammatory breast cancer.
KeywordsCholesterol metabolism Statins Radiation therapy Tumor-initiating cells FOXO3a HDL Inflammatory breast cancer
This work was supported by the National Institutes of Health R01CA138239-01 and 1R01CA180061-01, the State of Texas Grant for Rare and Aggressive Breast Cancer Research Program, the Inflammatory Breast Cancer Network Grant, and an institutional research grant from The University of Texas MD Anderson Cancer Center. The Research Animal Support Facility-Houston, Small Animal Imaging Facility, Flow Cytometry and Cellular Imaging Facility, and Research Histopathology Facility are supported in part by the National Institutes of Health through MD Anderson Cancer Center Support (core) Grant CA016672.
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Conflict of Interest
Omar M. Rahal and Wendy A. Woodward declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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