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Pitroda, Sean
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Translational Research
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My long-term vision is to transform the treatment of metastatic cancer through translational research that challenges the deeply held view that metastases are invariably widespread and incurable. I believe that a subset of patients with limited metastatic disease can be cured with appropriately tailored therapies—and that defining the biological underpinnings of this state is essential to advancing precision oncology. My laboratory employs integrative approaches combining molecular profiling of clinical metastases, advanced bioinformatics, immunologic analyses, and in vivo modeling to address two paradigm-defining questions: (1) What are the biological determinants that distinguish curable from incurable metastatic states? and (2) How can we systematically harness radiotherapy-immunotherapy synergy to overcome immune resistance mechanisms that limit curability? We were the first to demonstrate a biological basis for curable oligometastatic disease, showing that robust adaptive immune activation in concert with favorable clinical features predicts ~95% 10-year survival in colorectal cancer patients with resected liver metastases (Nature Communications 2018)—a finding validated in the randomized phase III New EPOC trial (JAMA Oncology 2023) and now being translated into clinical practice. Extending this framework across cancer types, we showed that tumor aneuploidy serves as a pan-cancer biomarker predicting immunotherapy response (Nature Genetics 2022) and that concurrent ablative radiotherapy enhances this response in highly aneuploid metastatic lung cancers (Nature Cancer 2022). Building on these clinical observations, we are now elucidating the mechanistic basis for how radiation interacts with immune-modifying therapies in patients. Our recent work identified radiation-induced amphiregulin as a critical mediator that reprograms myeloid cells toward immunosuppressive phenotypes, providing new targets to enhance the efficacy of combined radiation-immunotherapy approaches (Nature 2025). These discoveries are driving the development of molecular diagnostic tools now being deployed clinically to guide treatment selection.
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Pitroda, Sean