Fox Chase Cancer Center Philadelphia, Pennsylvania
Assistant Professor, Department of Radiation Oncology American Society for Radiation Oncology
Investigating combination therapy for metastatic triple negative breast cancer.
Triple-negative breast cancer (TNBC) is an aggressive disease that accounts for approximately 15% of breast cancer cases. It disproportionately affects women under 40, with an especially high incidence among Black and Hispanic women and those harboring a mutation of the BRCA1 gene. It carries a worse prognosis than other forms of breast cancer and often proves resistant to any form of single-agent therapy. This resistance means that clinicians treating TNBC must rely on combinations of existing therapeutic agents. The immunogenic property of radiation therapy, a property called the abscopal effect, was first detected over 50 years ago. High-dose radiation therapy (HDRT) delivered to a primary tumor was shown to elicit a systemic immune reaction resulting in shrinkage of distant metastatic tumors. A more recent discovery is that low-dose radiation therapy (LDRT), which can be safely delivered to multiple sites, is also immunogenic and can be combined with agents inducing immune checkpoint blockade (ICB) to exploit the body’s native defenses against metastatic disease.
Curaxin is a newly developed cancer drug that stimulates an intense immunologic response by activation of the necroptosis pathway, a programmed form of inflammatory cell death. The capacity of curaxin to trigger necroptosis in difficult to treat tumors makes it suitable for combining with LDRT and ICB. For her ASTRO award supported by BCRF, Dr. Shulman aims to test the benefits of various permutations of the HDRT/LDRT-ICB-curaxin combination in laboratory models of metastatic TNBC to assess the contribution of the necroptosis pathway to the observed tumor response. Demonstrating effectiveness of HDRT/LDRT-ICB-curaxin combination therapy in laboratory models would provide the basis for preliminary clinical trials of an entirely new approach to the treatment of metastatic TNBC.
Rebecca M. Shulman, MD is an Assistant Professor in the Department of Radiation Oncology at Fox Chase Cancer center. She graduated magna cum laude from New York University, where she majored in psychology, and attended medical school at the Lewis Katz School of Medicine at Temple University. She completed her residency training in radiation oncology at Fox Chase Cancer Center, where she contributed to numerous clinical and translational research studies. Throughout her training, she has directed and collaborated with programs devised to extend the inclusivity and global reach of medical education. Dr. Shulman’s research focuses on combining biological discoveries, including our expanding knowledge of inflammatory and immune cellular mechanisms, with the innovative techniques of precision radiotherapy to devise effective cancer treatments.
2023
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