Associate Professor, Radiation Oncology
University of Pennsylvania
Seeking to identify targets to improve response to immunotherapies.
Laboratory studies are conducted to understand how signals between cells can be therapeutically exploited to improve response to cancer immunotherapy.
These studies may lead to better therapies and biomarkers that can identify patients most likely to benefit from immunotherapy.
Interactions between breast cancer cells and cells in the tumor microenvironment drive tumor progression, drug resistance and metastasis. Stromal fibroblasts make up the majority of non-epithelial cells in the breast and are known to promote the aggressive characteristics of invasive breast cancers. How they do this, however, is not well understood.
Dr. Minn and team have identified a set of signaling events that occur when breast cells and stromal cells interact. These signals are more common in triple-negative breast cancer (TNBC) compared to estrogen receptor (ER)-positive tumors, possibly explaining the more aggressive and inflammatory nature of TNBC.
A key component of this reaction involves an artificial "wound response" that tricks the immune system to launch an immune attack, such as for an infection. The result is that the immune system busily "attacks" the artificial infection and the tumor cells go undetected.
Dr. Minn's team is investigating how these signals can be therapeutically exploited in both TNBC and ER-positive tumors. In particular, they will examine: 1) whether immunotherapies can take advantage of these inflammatory signals by resetting immune cell function to attack the tumor, and 2) if these inflammatory signals can serve as biomarkers to aid our understanding of the immune landscape of established tumors and/or identify patients who will benefit from immunotherapies.
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.