Titles and Affiliations
Chair, Immuno-Oncology Program
Director, Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation
Research area
Improving resistance to immunotherapies in breast cancer by targeting chronic inflammation.
Impact
Immunotherapy harnesses the power of the immune system to fight cancer and is one of the most significant recent advances in cancer medicine. For breast cancer, immunotherapy has demonstrated activity for certain subtypes such as triple-negative breast cancers; however, efficacy has unfortunately been lower compared to cancers such as melanoma and lung cancer. Even when immunotherapy initially works, tumors can develop resistance and relapse months or years later. Dr. Minn and his team are investigating how chronic inflammation, particularly through a signaling molecule called interferon, drives this acquired resistance. The team hypothesizes that prolonged exposure to interferon causes cancer cells to develop a kind of “inflammatory memory” that allows them to evade immune attack even after initially responding to therapy.
Progress Thus Far
Dr. Minn and his team are examining specific signaling pathways that intersect with chronic interferon activity and conducting broad screens of nearly all known genes to identify new drivers of resistance. They have found that acquired resistance can be prevented or reversed, either through existing drugs or through new therapeutic targets still being developed. Using a cell-tracking technique that follows groups of related cancer cells over time, the team showed that drug combinations targeting these inflammatory pathways can shift cancer cells away from resistance and make them more vulnerable to immunotherapy. This work suggests it may be possible to prevent resistance from developing in the first place, rather than trying to overcome it after it has already taken hold.
What’s next
In the next phase of their research, the team will complete a genome-wide screen, a method that tests nearly all known genes at once, to identify new ways to reverse acquired resistance driven by chronic inflammation and interferon signaling. Genes identified through this screen may represent new drug targets for restoring and sustaining response to immunotherapy. The team will also extend their work to understand how antibody-drug conjugates (ADCs), a class of cancer drugs that deliver toxic agents directly to cancer cells, can be effectively combined with immunotherapy. Chronic inflammation may also affect how well ADCs work, particularly in combination with immune-based therapies.
Biography
Andy J. Minn, MD, PhD is the Chair of the Immuno-Oncology Program at Memorial Sloan Kettering Cancer Center. He is also the Director of the Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation and Project Member at the Parker Institute for Cancer Immunotherapy. He received his MD and PhD from the University of Chicago and completed his residency in radiation oncology and post-doctoral training at Memorial Sloan Kettering Cancer Center.
His laboratory is focused on understanding the regulation and function of anti-viral signaling pathways, such as interferon and pattern recognition receptors, in cancer progression, immunotherapy response, and immunomodulation. They have discovered that activation of anti-viral signaling is widespread across multiple cancer types and often involves nucleic acid sensing, endogenous RNAs, exosomes, and interferon networks. Thus, endogenous molecules that participate in “virus mimicry” are pervasive in human cancer. They are investigating how anti-viral and pattern recognition receptors are activated in cancer, both cell intrinsically and through the tumor microenvironment, and their functional significance).
