Stephan Patrick, Ph.D., associate professor of Oncology at the Wayne State University School of Medicine and member of the Molecular Therapeutics Program at the Barbara Ann Karmanos Cancer Institute, has been selected as the 2019 winner of the Anthony and Joyce Danielski Kales Endowed Faculty Award for Innovative Cancer Researcher.

His research focuses on studying how cancer cells respond to chemotherapy to improve treatment options for patients.

“I was shocked, but at the same time I am deeply honored,” he said upon learning he had won the honor.

Dr. Patrick began his doctoral program in 1994, and at that time was “drawn to platinum-based drugs in trying to understand how they function and determine how cancer cells become resistant to therapy.”

The Kales Award was created in 2012 at the Wayne State University School of Medicine to recognize exemplary and innovative cancer research. It 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.

Dr. Patrick was honored at at Oct. 24 Karmanos’ Grand Rounds ceremony. He spoke about his research, specifically the publication for which he was recognized, “Identification and Characterization of Synthetic Viability with ERCC1 Deficiency in Response to Interstrand Crosslinks in Lung Cancer.” The article was published in Clinical Cancer Research in 2018.

The research was executed by a team from the Molecular Therapeutics Program and Biostatistics Core at Karmanos Cancer Institute and Wayne State University. His co-authors include WSU graduate students, Joshua R. Heyza, Ph.D., and Donovan Watza, Ph.D.; research technicians, Hao Zhang and Wen Lei; and faculty colleagues, Wei Chen, Ph.D.; Jessica Back, Ph.D.; Ann Schwartz, Ph.D., M.P.H.; and Gerold Bepler, M.D., Ph.D. president and chief executive officer of the Karmanos Cancer Institute and chair of WSU Oncology.

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. Loss of ERCC1 and its utilization as a biomarker for platinum response in lung cancers has been investigated previously by numerous researchers, however, there has been controversy and a lack of clinical value to date. Importantly, the study conducted by Dr. Patrick and colleagues uncovered the importance of the p53 gene in mediating sensitivity to platinum-based chemotherapy in response to 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 team identified a synthetic viable phenotype in ERCC1-deficient cells when p53 is mutated. Of utmost importance, the team identified novel drug combinations that would overcome the drug tolerance in the lung cancer cell line models and restore a hypersensitive phenotype.

Collaborating with Dr. Bepler since the beginning of his career at Karmanos, Dr. Patrick and his team are avidly working to initiate clinical trials, starting with lung cancer and expanding to other cancers from the research conducted. In addition, they are working to publish a follow-up paper to announce a new drug combination to treat platinum-tolerant cancer cells that result in hypersensitization to platinum-based chemotherapy.

Dr. Patrick noted that understanding the molecular mechanisms of resistance to DNA cross-linking agents can be linked to improving patient responses to platinum-based chemotherapy. “Targeting DNA repair pathways to enhance platinum-based chemotherapy will make a significant contribution to the treatment of cancers.”

Reflecting on future research, Dr. Patrick said that researchers are “trying to devise new treatment options for the 10 to 15 percent of non-small cell lung cancers that are ERCC1 deficient and p53 mutated, and which do not typically respond well to platinum-based chemotherapy.” He further noted that adding another drug to the regimen of this population of NSCLCs would potentially enhance the effect of platinum-based drugs, which will remain part of the standard of care. His research significantly influences the chemotherapy options not only for lung cancer exclusively, but for many cancers with low ERCC1, most commonly seen in ovarian cancer.

Dr. Patrick added, “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.”