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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 is focused on defining 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: Dr. Minn will continue to examine how genes function to control immune checkpoint inhibition and additional vulnerabilities that can be targeted to enhance the therapeutic impact.
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: Immune checkpoint inhibitors (CPI) are an exciting new class of immunotherapy drugs that have resulted in unprecedent responses and improvement in survival for certain cancers. In breast cancer, this treatment has demonstrated activity for certain subtypes, such as triple-negative breast cancer, but efficacy has generally been lower compared to other cancers such as melanoma and lung cancer. Therefore, identifying barriers that improve response and prevent resistance to these therapies is an important goal. Dr. Minn’s lab is boldly pursuing innovative strategies to broaden the benefit of immunotherapies for breast cancer.
Current investigation: Dr. Minn has revealed the interferon (IFN) signaling pathway as a potentially actionable target that regulates the response to immunotherapy. Dr. Minn will continue to focus on optimizing the methods to inhibit cancer cell IFN signaling to restore immune function.
What he’s learned so far: Over the course of the last three years of BCRF funding, Dr. Minn has made significant progress in identifying key factors underlying the ability of tumors cells to evade the immune response. Specifically, he has shown that interactions between tumor cells and the cells in the tumor microenvironment lead to activation of inflammatory pathways that suppress the immune system, shielding the tumor from cancer-killing immune cells. These findings led him to the discovery that the interferon (IFN) pathway (which usually triggers a protective response by the immune system) mediates suppression of the immune system by cancer cells similar to an anti-viral reaction. Furthermore, he and his colleagues have identified changes that occur with chronic IFN signaling and that result in resistance to immune checkpoint inhibitors. Thus, these studies have revealed the IFN signaling pathway as a potentially actionable target that regulates the response to immunotherapy. He and his colleagues have also identified two related and targetable signaling pathways that limit the efficacy of immune checkpoint inhibitors.
What’s next: Dr. Minn will continue to focus on optimizing the methods to inhibit cancer cell IFN signaling to restore immune function. In addition, his team will conduct in depth characterizations of specific IFN signaling genes which they have previously shown to control cell death and inflammation. They will address outstanding questions, including:
- Which of these genes are critical for IFN-driven resistance to immunotherapy?
- How do these genes function to control immune checkpoint inhibition?
- Are there additional vulnerabilities in the action of these genes that can be targeted to enhance the therapeutic impact of targeting IFN signaling?
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