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.
Frontera ED, RM Khansa, DL Schalk, LE Leakan, TJ Guerin-Edbauer, M Ratnam, DH Gorski, and CL Speyer. IgA Fc-folate conjugate activates and recruits neutrophils to directly target triple-negative breast cancer cells. Breast Cancer Res Treat. 2018 Epub date: 2018/08/30.
Holowatyj AN, ML Cote, JJ Ruterbusch, K Ghanem, AG Schwartz, FD Vigneau, DH Gorski, and KS Purrington. Racial Differences in 21-Gene Recurrence Scores Among Patients With Hormone Receptor-Positive, Node-Negative Breast Cancer. J Clin Oncol 2018;36:652-8.
Speyer CL, MA Bukhsh, WS Jafry, RE Sexton, S Bandyopadhyay, and DH Gorski. Riluzole synergizes with paclitaxel to inhibit cell growth and induce apoptosis in triple-negative breast cancer. Breast Cancer Res Treat 2017;166:407-19.
Henry NL, TM Braun, TM Breslin, DH Gorski, SM Silver, and JJ Griggs. Variation in the use of advanced imaging at the time of breast cancer diagnosis in a statewide registry. Cancer 2017;123:2975-83.
Henry NL, TM Braun, HY Ali, K Munir, SM Silver, DH Gorski, TM Breslin, and JJ Griggs. Associations between use of the 21-gene recurrence score assay and chemotherapy regimen selection in a statewide registry. Cancer 2017;123:948-56.
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, DH Gorski, and PC Albertsen. Trends in Metastatic Breast and Prostate Cancer--Lessons in Cancer Dynamics. N Engl J Med 2015;373:1685-87.
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