@article{660ecdfee6414951b42b2aa478cc04c1,
title = "Computational Drug Repositioning Identifies Statins as Modifiers of Prognostic Genetic Expression Signatures and Metastatic Behavior in Melanoma",
abstract = "Despite advances in melanoma treatment, more than 70% of patients with distant metastasis die within 5 years. Proactive treatment of early melanoma to prevent metastasis could save lives and reduce overall healthcare costs. Currently, there are no treatments specifically designed to prevent early melanoma from progressing to metastasis. We used the Connectivity Map to conduct an in silico drug screen and identified 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) as a drug class that might prevent melanoma metastasis. To confirm the in vitro effect of statins, RNA sequencing was completed on A375 cells after treatment with fluvastatin to describe changes in the melanoma transcriptome. Statins induced differential expression in genes associated with metastasis and are used in commercially available prognostic tests for melanoma metastasis. Finally, we completed a chart review of 475 patients with melanoma. Patients taking statins were less likely to have metastasis at the time of melanoma diagnosis in both univariate and multivariate analyses (24.7% taking statins vs. 37.6% not taking statins, absolute risk reduction = 12.9%, P = 0.038). These findings suggest that statins might be useful as a treatment to prevent melanoma metastasis. Prospective trials are required to verify our findings and to determine the mechanism of metastasis prevention.",
author = "Yu, {Wesley Y.} and Hill, {Sheena T.} and Chan, {E. Ricky} and Pink, {John J.} and Kevin Cooper and Sancy Leachman and Amanda Lund and Rajan Kulkarni and Bordeaux, {Jeremy S.}",
note = "Funding Information: The authors would like to acknowledge Jennifer Arnold, Simone Edelheit, and Alexander Miron for technical assistance; Amanda Davies for regulatory guidance; and John Pounardjian for assistance with funding. This publication was made possible by funding from the Case Comprehensive Cancer Center (Cleveland, OH), the Clinical and Translational Science Collaborative of Cleveland (UL1TR002548), and the National Center for Advancing Translational Sciences component of the National Institutes of Health and National Institutes of Health Roadmap for Medical Research. This research was also supported by the Translational Research Shared Resource and the Genomics Shared Resource of the Case Comprehensive Cancer Center (P30 CA043703). RK acknowledges support from the Melanoma Research Alliance , the American Cancer Society , the Cancer Research Institute , the Department of Defense Prostate Cancer Research Program award (W81XWH-17-1-0098), and the Department of Defense Peer Reviewed Cancer Research Program award (W81XWH-17-1-0514). The study was approved by the University Hospitals Institutional Review Board (STUDY20200545) Funding Information: WYY has received research funding from SkylineDx. The remaining authors state no conflict of interest. Funding Information: The authors would like to acknowledge Jennifer Arnold, Simone Edelheit, and Alexander Miron for technical assistance; Amanda Davies for regulatory guidance; and John Pounardjian for assistance with funding. This publication was made possible by funding from the Case Comprehensive Cancer Center (Cleveland, OH), the Clinical and Translational Science Collaborative of Cleveland (UL1TR002548), and the National Center for Advancing Translational Sciences component of the National Institutes of Health and National Institutes of Health Roadmap for Medical Research. This research was also supported by the Translational Research Shared Resource and the Genomics Shared Resource of the Case Comprehensive Cancer Center (P30 CA043703). RK acknowledges support from the Melanoma Research Alliance, the American Cancer Society, the Cancer Research Institute, the Department of Defense Prostate Cancer Research Program award (W81XWH-17-1-0098), and the Department of Defense Peer Reviewed Cancer Research Program award (W81XWH-17-1-0514). The study was approved by the University Hospitals Institutional Review Board (STUDY20200545), The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the funding institutions. Conceptualization: WYY; Data Curation: STH, ERC, JJP, WYY; Formal Analysis: STH, ERC, SL, AWL, WYY; Funding Acquisition: JJP, WYY; Investigation: STH, ERC, JJP, WYY; Project Administration: WYY; Resources: JJP, WYY; Software: ERC, WYY; Supervision: JSB, KC, SL, AWL, RK, WYY; Visualization: STH, ERC, WYY; Writing - Original Draft Preparation: STH, WYY; Writing - Review and Editing: ERC, JJP, JSB, AWL, SL, RK, WYY Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = jul,
doi = "10.1016/j.jid.2020.12.015",
language = "English (US)",
volume = "141",
pages = "1802--1809",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "7",
}