MD, Johns Hopkins University
Assistant Professor, Medicine (Hematology/Oncology)
Cancer Therapeutics Program Co-Leader
I. The role of autophagy inhibition in cancer therapy: Phase I clinical trials My previous preclinical studies have found that autophagy, a process by which cancer cells degrade their own intracellular organelles, can allow tumor cells to survive therapeutic stresses such as chemotherapy. Autophagy inhibition with the drug hydroxychloroquine can enhance the efficacy of a number of existing cancer therapies in preclinical studies. Based on these data, we have developed protocols for four phase I clinical trials combining hydroxychloroquine with existing anticancer therapies in both advanced solid tumors and hematological malignancies.
II. The role of autophagy inhibition in cancer therapy: laboratory studies In our laboratory, we are developing pharmacodynamic assays to detect autophagy inhibition in patients enrolled on the phase I clinical trials. Pharmacokinetic and genetic studies using patient materials have also be incorporated into these clinical trials in order to characterize the effects of hydroxychloroquine on autophagy in patients and to identify patient subsets which may benefit more or less from this therapeutic strategy. Our laboratory studies will also focus on identifying novel autophagy modulators and characterizing their effects in cancer cell lines and mouse models.
III. Improving the efficacy of chemotherapy with sorafenib Working within the Developmental Therapeutics program, Melanoma Program and GU Oncology Program we have launched a series of phase I and phase II trials to determine the activity and tolerability of combining the oral multikinase inhibitor sorafenib with chemotherapy in chemotherapy-refractory malignancies. The clinical trials include a completed phase II trial of temozolomide and sorafenib in patients with advanced melanoma and a currently accruing phase II trial of docetaxel and sorafenib in patients with androgen-independent prostate cancer.
» Developmental Therapeutics (Phase I & II)
Urologic Cancer Program
Melanoma and Pigmented Lesion Program
» Pigmented Lesion Clinic
» Urologic Cancer
American Association for the Advancement of Science
American Association for Cancer Research
American Society of Clinical Oncology
Internal Medicine, Brigham and Women's Hospital
Hematology-Oncology, University of Pennsylvania, Philadelphia
Hematology Oncology, 2006
Internal Medicine, 2003
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