Dr. DeMatteo is the Vice Chair of the Department of Surgery at Memorial Sloan Kettering Cancer Center. Clinically, he specializes in the treatment of hepatopancreatobiliary cancers and gastrointestinal stromal tumor (GIST), the most common human sarcoma. His research has focused on the immunologic,…
more molecular, and clinical aspects of GIST. He has been a pioneer in the investigation of the immune response to GIST, finding that imatinib (which inhibits KIT and PDGFRA oncoproteins) also works unexpectedly by reducing tumor cell production of the immunosuppressive enzyme IDO. In a genetically engineered mouse model, he showed that imatinib synergizes with the anti-CTLA4 immune modulator ipilimumab, justifying a Phase I National Cancer Institute (NCI) clinical trial. He demonstrated that intratumoral macrophages in human GIST have anti-tumoral (M1) properties, leading to a general reassessment of the function of intratumoral macrophages, which were previously thought to be always pro-tumoral. His lab discovered that GIST compensates during KIT inhibition by upregulating MET, which can be targeted for additional therapeutic effect. He correlated the specific types of oncogene mutations in GIST to clinical outcome in over 500 patients. He created an online nomogram to predict tumor recurrence following the resection of GIST and select patients for adjuvant molecular therapy. He led the 3 national clinical trials (2 sponsored by the NCI) testing postoperative imatinib in GIST. One trial led to FDA approval of imatinib as an adjuvant therapy and changed the standard of care worldwide. He has also made numerous contributions to our understanding of liver immunology.
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