His findings influence chemotherapy options for several cancers, including lung and ovarian
Stephan Patrick, Ph.D., an associate professor in the Department of Oncology at the Wayne State University School of Medicine and member of the Molecular Therapeutics Program at WSU and the Barbara Ann Karmanos Cancer Institute, is the recipient of the 2019 Anthony and Joyce Danielski Kales Endowed Faculty Award for Innovative Cancer Researcher.
“I was shocked, but at the same time I am deeply honored,” he said of receiving the award.
Dr. Patrick studies how cancer cells respond to chemotherapy to improve treatment options for patients.
Dr. Patrick will be honored at Karmanos' Grand Rounds ceremony on Oct. 24 in the Hudson Webber Cancer Research Center's Wertz Auditorium in Detroit. He will speak about his research, including the publication for which he is being recognized, "Identification and Characterization of Synthetic Viability with ERCC1 Deficiency in Response to Interstrand Crosslinks in Lung Cancer,” published in Clinical Cancer Research in 2018.
Dr. Patrick and his colleagues identified a combative way to exploit cancer-specific loss of ERCC1, a DNA endonuclease that plays a critical role in mediating platinum-based chemotherapy response. Many cancer treatments, especially for lung cancer, include a platinum-based regimen, so it is important to identify biomarkers of platinum-based chemotherapy response, he said. Loss of ERCC1 and its utilization as a biomarker for platinum response in lung cancers has been investigated before, however, there has been controversy and a lack of clinical value to date. Dr. Patrick and colleagues have now uncovered the importance of the p53 gene in mediating sensitivity to platinum-based chemotherapy in response to this ERCC1 deficiency. Also known as the “tumor suppressor protein," p53 helps control apoptosis and mediates cell-cycle control; however, the loss of p53 uncovers an alternative, error-prone pathway that enables cells to tolerate platinum-based chemotherapy with ERCC1 loss.
The award, created in 2012 at WSU to recognize exemplary and innovative cancer research, is supported by the Drs. Anthony and Joyce Danielski Kales Endowed Faculty Award for Innovative Cancer Research Endowment. Selection is based on a comprehensive review of published articles within the previous year.
The research was executed by a team from the Molecular Therapeutics Program and Biostatistics Core at Wayne and Karmanos. His co-authors include WSU graduate students Joshua R. Heyza and Donovan Watza; research technicians, Hao Zhang and Wen Lei; and Oncology Associate Professor Wei Chen, Ph.D.; Research Scientist Jessica Back, Ph.D.; Professor Ann Schwartz, Ph.D., M.P.H.; and Karmanos President and Chief Executive Officer Gerold Bepler, M.D., Ph.D.
Together, the team identified a synthetic viable phenotype in ERCC1-deficient cells when p53 is mutated, as well as novel drug combinations that would overcome the drug tolerance in the lung cancer cell line models and restore a hypersensitive phenotype.
Dr. Patrick and his team are working to initiate clinical trials, starting with lung cancer, and plan to publish a new drug combination to treat platinum-tolerant cancer cells that result in hypersensitization to platinum-based chemotherapy.
His research significantly influences the chemotherapy options for not just lung cancer exclusively, but for many cancers with low ERCC1, most commonly seen in ovarian cancer. "To achieve the best response, exploiting the DNA repair deficiencies in cancer cells and targeting them with specific chemotherapeutic drugs is critical to the future of platinum-based therapy,” he said.