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Norman Wolmark, MD
Professor, Department of Surgery
University of Pittsburgh School of Medicine
Director, National Cancer Institute Cooperative Group Clinical Trials
University of Pittsburgh Hillman Cancer Center
On behalf of the National Surgical Adjuvant Breast and Bowel Project (NSABP)
Goal: To understand what drives treatment resistance in patients with HER2-positive breast cancer.
Impact: Dr. Wolmark is conducting laboratory studies to understand why some HER2-positive cancers respond to HER2-targeted drugs and others do not. His findings could inform the development of combination treatments that overcome resistance and improve outcomes for patients with this disease.
What’s next: He and his colleagues will continue to study breast cancer cells that express an altered form of HER2, called p95HER2, that drives tumor progression. They will also identify
resistance biomarkers for HER2-positive metastatic breast cancer patients whose tumors did not respond to standard therapy.
While there are several targeted therapies available for HER2-positive breast cancer, resistance to these treatments is a major clinical challenge. In order to overcome drug resistance and improve patient response, a greater understanding of HER2-targeted drug resistance is needed. Dr. Wolmark’s team is identifying resistance markers and determining optimal drug combinations for more effective treatment of HER2-positive breast cancer.
Full Research Summary
Research Area: Seeking strategies to reduce resistance to HER2-targeted therapies and improve outcomes in patients with this disease.
Impact: Therapies such as trastuzumab have revolutionized the treatment of HER2-positive breast cancer. Trastuzumab and other HER2-targeted therapies block the pro-tumorigenic actions of HER2 on cancer cells and stimulate an immune response directed against the cells. Nevertheless, only a subset of patients with HER2-positive breast cancer experience a robust response and there is a pressing need to understand why some do not. Dr. Wolmark’s BCRF research aims to discover markers and elucidate mechanisms of resistance to these therapies with the goal of identifying potential companion drugs to prevent it.
Current research: Dr. Wolmark’s team is continuing ongoing work to target an altered form of HER2 called p95HER2, that cannot be targeted by standard-of-care therapeutic antibodies such as trastuzumab. Their goal is to develop new strategies to re-invigorate the immune system to overcome this action of p95HER2. Additionally, they are identifying biomarkers that define HER2-positive tumors that are resistant to standard treatment.
What he’s learned so far: The team has initiated the development of tools to 1) identify the mechanism that may be responsible for why some tumors do not respond to anti-HER2 therapy, and 2) to identify new treatment regimens to overcome these mechanisms of resistance. These tools include the development of an antibody that specifically recognizes p95HER2 and the development of novel model systems from patient tumors to test new therapeutic regimens.
What’s next: Dr. Wolmark and his team will identify resistance biomarkers for HER2-positive metastatic breast cancer patients whose disease did not respond to anti-HER2 therapy by using the tissues, collected in NSABP clinical trial FB-10. Patients enrolled in FB-10 were treated with a new anti-HER2 regimen because they failed treatment with trastuzumab plus pertuzumab, another anti-HER2 antibody. They will also analyze genes that are expressed and activate signaling pathways in response to treatment.
Dr. Norman Wolmark, MD, is Chairman of NSABP Foundation, a not-for-profit academic research organization with a nearly 60-year history of conducting ground-breaking research studies in breast and colorectal cancer.
He is also Professor and Chairman of Human Oncology at Drexel University School of Medicine. Dr. Wolmark received his medical degree from McGill University of Montreal, and he completed his residency at the University of Pittsburgh. He served a fellowship in Surgical Oncology at Memorial Sloan Kettering Cancer Center, and he later became a cancer expert at the Surgery Branch of the National Cancer Institute.
Dr. Wolmark belongs to numerous prestigious organizations including the American Society of Clinical Oncology, the American Association of Cancer Research, and the American Surgical Association.
Over his near 45-year tenure as a cancer researcher, Dr. Wolmark is extensively published, with more than 400 scientific journal articles and book chapters in print. He is a widely sought-after speaker and lecturer in his field and serves on the editorial board of the Journal of Women’s Cancer, The Journal of Clinical Oncology, and numerous advisory boards, and as an advisor to oncology programs, societies, and institutes throughout the United States and abroad.
Devoted to the evolution of large randomized clinical trials for the treatment and prevention of breast and bowel cancers, he is also a reviewer for the Journal of Clinical Oncology and the New England Journal of Medicine, and he is an editorial board member of the Journal of Women's Cancer and Clinical Breast Cancer.