John Ebos: 'Unexpected collateral effects of angiogenesis and immunecheckpoint inhibition: Impact on metastasis, resistance, and biomarkers
Organisateur : Eddy Pasquier
Lieu : IPC2
Roswell Park Cancer Institute, Buffalo, NY
One consistent (and often frustrating) aspect of cancer research is learning that a preclinical ‘breakthrough’ did not eventually lead to a new therapeutic benefit for patients. This may stem, at least in part, from the fact that new drugs are often tested in patients with advanced metastatic disease while mouse models typically examine only localized ‘primary’ tumors. This testing gap may explain why some inhibitors of the tumor microenvironment, including angiogenesis and immune-checkpoint inhibitors, often poorly predict why a drug may succeed (or fail) in clinical trials. My laboratory aims to study VEGF and PD-1 pathway inhibition in mouse models that recapitulate the steps of metastasis, including initial primary tumor growth, surgery, and the generation of spontaneous distant disease. Our studies have uncovered evidence that treatments can often have opposite effects, perhaps explaining why efficacy in patients is often far more modest than predicted. This lecture will focus on recent results showing that off-target ‘collateral’ effects of therapy include a broad array of secretory changes that can contribute to treatment failure for both VEGF and PD-1 targeting agents and may provide a guide to predict patient outcomes.
John Ebos, PhD
Assistant Professor of Oncology in the Departments of Cancer Genetics and Medicine at Roswell Park Comprehensive Cancer Center (RPCC), and is a member of the graduate faculty in the Department of Pharmacology and Therapeutics at the State University of New York at Buffalo.