David H. Gorski
David H. Gorski, MD, PhD, FACS
Professor and Chief, Breast Surgery Section
Michael and Marian Ilitch Department of Surgery
Wayne State University School of Medicine
Medical Director, Alexander J. Walt Comprehensive Breast Center
Barbara Ann Karmanos Cancer Institute
4100 John R St.
Detroit, MI 48201
Office: +1 (313) 576-8490
Laboratory: +1 (313) 576-9423
Dr. Gorski is interested in three areas of research, two translational, and one clinical. The translational research projects involve developing better systemic treatments for breast cancer, and the clinical project involves his role as the co-director of the Michigan Breast Oncology Initiative (MiBOQI):
1. Repurposing riluzole to treat breast cancer, particularly triple negative breast cancer. Triple negative breast cancer is an aggressive subtype for which there is no targeted treatment and cytotoxic chemotherapy is nearly always required. Thus, there is an urgent need for a “Tamoxifen for triple negative breast cancer”, an oral drug with low toxicity. We believe that we have identified a drug (riluzole) that can potentially be repurposed to achieve this goal, as it is an oral drug with very low toxicity and is already FDA-approved for the treatment of the degenerative neurologic disease amyotrophic lateral sclerosis. However, there remain pressing questions about riluzole's mechanism of action that need to be clarified prior to undertaking clinical trials. When we originally identified the anti-TNBC activity of riluzole, it was thought that its antitumor effect derived from its ability to inhibit glutamatergic signaling through metabotropic glutamate receptor-1 (mGluR1) and possibly others. However, we have recently discovered that riluzole activity does not correlate tightly with mGluR1 expression in breast cancer cell lines. Riluzole also inhibits voltage-gated sodium channels, which have recently been implicated in breast cancer progression. We currently have a Department of Defense Breakthrough Award to do studies clarifying the mechanism of riluzole in inhibiting breast cancer growth as a prelude to clinical trials.
2. Tumor glucocorticoid receptor status as a predictive marker to improve outcome of chemotherapy in triple negative breast cancer (collaborate tion with Dr. Manohar Ratnam). The synthetic asteroid dexamethasone is often used to premedicate patients receiving chemotherapy for breast cancer because taxanes, a mainstay in breast cancer systemic therapy, can cause severe hypersensitivity reactions. Unfortunately, because dexamethasone stimulates the glucocorticoid receptor (GR), it can antagonize the effects of the very chemotherapy for which it is used to premedicate. Dr. Ratnam and Dr. Gorski are therefore collaborating to use GR as a predictive biomarker for response to treatment, the goal being a clinical trial in order to validate it as a marker.
3. Quality Improvement. Dr. Gorski served as co-director of MiBOQI, a collaborative quality initiative (CQI) involving 25 hospitals in Michigan, from 2013-2016, during which he oversaw or collaborated on several QI initiatives, including postmastectomy radiation therapy, time to chemotherapy after surgery, the use of multigene predictive assays to guide chemotherapy decisions, and the overuse of advanced imaging. Although MiBOQI no longer exists, Dr. Gorski is still interested in local QI initiatives at KCI and the DMC.
Other interests: As the managing editor of Science-Based Medicine (SBM), a weblog devoted to discussing the science of medicine,Dr. Gorski is very interested in science communication and critical thinking, and interested students are welcome to publish in SBM under Dr. Gorski’s guidance to hone their writing skills for lay audiences.
Speyer CL, Nasar M, Sachem AH, Bukhsh M, Jafry WS, Khansa R, Gorski DH. Riluzole mediates anti-tumor properties in breast cancer cells independent of metabotropic glutamate receptor-1 (mGluR1). Breast Cancer Res Treat 2016;157:217-28.
Holowatyj AN, Ruterbusch JJ, Ratnam M, Gorski DH, Cote ML. HER2 status and socioeconomic disparities in luminal breast cancers. Cancer Med 2016;5:2109-16.
Welch, HG, Gorski DH, Albertsen PC. Trends in Metastatic Breast and Prostate Cancer--Lessons in Cancer Dynamics. N Engl J Med 2015;373:1685-7.
Gorski DH. Integrative oncology: really the best of both worlds? Nat Rev Cancer 2014;14:692-700.
Gorski DH, Novella SP. Clinical trials of integrative medicine: testing whether magic works? Trends Mol Med. 2014;20:473-6.
Speyer CL, Hachem AH, Assi AA, Johnson JS, DeVries JA, Gorski DH. Metabotropic glutamate receptor-1 as a novel target for the antiangiogenic treatment of breast cancer. PLoS One. 2014;9:e88830.
Banda M, Speyer CL, Semma SN, Osuala KO, Kounalakis N, Torres Torres KE, Barnard NJ, Kim HJ, Sloane BF, Miller FR, Goydos JS, Gorski DH. Metabotropic glutamate receptor-1 contributes to progression in triple negative breast cancer. PLoS One. 2014;9:e81126.
Kaur H, Mao S, Shah S, Gorski DH, Krawetz SA, Sloane BF, Mattingly RR. Next-generation sequencing: a powerful tool for the discovery of molecular markers in breast ductal carcinoma in situ. Expert Rev Mol Diagn. 2013;13:151-65.
Speyer CL, Smith JS, Banda M, DeVries JA, Mekani T, Gorski DH. Metabotropic glutamate receptor-1: a potential therapeutic target for the treatment of breast cancer. Breast Cancer Res Treat. 2012;132:565-73.
Chen Y, Banda M, Speyer CL, Smith JS, Rabson AB, Gorski DH. Regulation of the expression and activity of the antiangiogenic homeobox gene GAX/MEOX2 by ZEB2 and microRNA-221. Mol Cell Biol. 2010;30:3902-13.
Education and Training:
MD (1988): University of Michigan, Ann Arbor, Michigan
PhD (1994): Case Western Reserve University, Cleveland, Ohio
Residency (1996): General Surgery, University Hospitals of Cleveland/Case Western Reserve University
Fellowship (1999): Surgical Oncology, University of Chicago
Cancer Biology Courses Taught:
CB7300 Special Topics F31 Grant Writing Course
CB7700 Recent Developments in Cancer Biology