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Andy Minn, MD, PhD
Associate Professor, Radiation Oncology
Director, Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation
University of Pennsylvania
Goal: To discover ways to improve effectiveness of immunotherapy for breast cancer patients.
Impact: Dr. Minn’s work is focused on the ways in which cancer cells resist immune-based treatments. His findings could help identify those patients who are most likely to respond to this type of treatment and may also reveal ways to improve immunotherapy so that it benefits more patients.
What’s next: Having discovered pathways that allow breast cancers to “outsmart” the effects of immunotherapy, he and his team will now study whether blocking these pathways could improve treatment response.
Immunotherapy has greatly improved responses and survival for those with certain types of cancer such as melanoma and lung cancer. Most breast cancer patients, however, have not had the same benefit. Dr. Minn has identified signaling pathways that normally tell the immune system to fight cancer but can be co-opted by cancer cells to limit the anti-tumor immune response. It is possible that interfering with these pathways could improve the effectiveness of immunotherapy.
Full Research Summary
Research area: Exploring novel strategies to improve the efficacy of immunotherapy in breast cancer.
Impact: Immunotherapies using immune checkpoint blockade agents has demonstrated activity in certain breast cancer subtypes. However, response rate in breast cancer remains low. Dr. Minn has discovered that cancers can mimic certain features of viral infections to minimize immune-mediated attack. In addition, a large percentage of breast cancer patients have tumors that express anti-viral genes. His team is investigating the mechanism of anti-viral signaling pathways in breast cancer and how interference in these pathways may restore immune function against cancer cells and improve the efficacy of immunotherapy.
Current investigation: Dr. Minn and his team are studying how anti-viral signaling pathways become programmed into the DNA of breast and other cancers. In addition, they are examining how blocking these pathways can restore anti-tumor immune response.
What he’s learned so far: Dr. Minn has investigated the role of anti-viral signaling pathways in the response of breast cancer to immunotherapy. They have found two related and targetable signaling pathways that limit the efficacy of immune checkpoint blockade. In addition, they show that blocking these pathways can restore immune function against cancer cells thus preventing breast cancer from mimicking viral infections.
What’s next: The team will continue to pursue innovative strategies to broaden the benefit of immunotherapies to breast cancer treatment. Specifically, they will focus on finding ways to prevent breast cancer from mimicking viral infections.
Dr. Minn is an Associate Professor in the Department of Radiation Oncology and Abramson Family Cancer Research Institute at the University of Pennsylvania. He received his MD and PhD from the University of Chicago, and finished his residency in radiation oncology and his post-doctoral training at Memorial Sloan-Kettering Cancer Center.
His laboratory is focused on understanding how breast cancers and other cancer types become resistant to both conventional therapies and to immunotherapies, and how resistance can be overcome. His work has unexpectedly revealed that pathways typically activated by viruses are among the important pathways cancers use to acquire their resistant properties (as well as other aggressive features). This raises two questions: 1) what is mimicking a viral infection in cancer, and 2) how does the activation of anti-viral signaling influence whether cancers respond or relapse after therapy?
Through the integration of “big data” and other genome-wide approaches, recent efforts are providing insight into these questions. These insights include the discovery of endogenous molecules that masquerade as viruses, and how these virus mimics orchestrate anti-viral responses to marshal the immune system and influence treatment outcomes. By gaining a deep mechanistic understanding, an overarching objective of Dr. Minn’s research is to manipulate these pathways to improve therapeutic efficacy and to inform the design of clinical trials.
BCRF Investigator Since
The William P. Lauder Award