Discovery of Tumor and Treatment Response Biomarkers

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As a practicing radiation oncologist, seeking to integrate my laboratory and clinical efforts into a cohesive translational research program, I have focused my clinical practice on the care of patients with metastatic cancers, for whom radiation may be beneficial. These radiation treatments are provided in the setting of their care at NIH, which often includes treatment with some form of immune-directed therapy. This patient population is size-able, and these patients comprised nearly one third of all of the patients treated in the NIH Radiation Oncology Branch across the past two years. To best be able to determine what liquid biopsy or biofluid biomarkers correlate with responses to treatment, the translational research efforts of this project are following a two-pronged approach: 1) collaborating with medical and surgical oncology colleagues at NIH to investigate EVs as biomarkers for tumor status as part of those collaborators' existing protocols, and 2) developing new clinical protocols to capture information and samples from this patient population in a more cohesive and informative manner. Both of these approaches are supported by and provide support to the CCR's clinical translational mission and the basic scientific work ongoing in the Translational Nanobiology Section for the study of EV repertoires. The entirety of this project arises in the context of providing best available care to our patients, whether standard of care or on clinical trial, while seeking to identify better ways to tailor care for individual patients. This effort has led to publication of a number of clinical trials (two clinical trials of radiation and immunotherapy for the treatment of GI malignancies with Tim Greten), ongoing progress of several additional clinical trials (with Dickran Kazandjian, Andrea Apolo, and others), and the development of multiple additional new clinical trials that will be submitted for CCR review in the upcoming year.