George D. Demetri, MD
Senior Vice President for Experimental Therapeutics
Professor of Medicine, Harvard Medical School
Office phone: 617-632-6563
Preferred contact method: office phone
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Soft tissue sarcoma, Bone sarcomas, Gastrointestinal stromal tumors (GIST), Developmental therapeutics
Area of ResearchMolecular Targeted Agents and Signal Transduction Inhibitors
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
Dr. Demetri is director of the Center for Sarcoma and Bone Oncology at DFCI, director of the Ludwig Center at Dana-Farber/Harvard Cancer Center, and executive director for Clinical and Translational Research at the Ludwig Institute for Cancer Research.
- Claire W. and Richard P. Morse Research Award, 2005
- Emil J. Freireich Award in Clinical Cancer Research, 2002
- Focused Giving Program Award, Johnson and Johnson Foundation, 1993
ResearchMolecular Targeted Agents and Signal Transduction Inhibitors
Sarcomas are a microcosm of solid tumor oncology: different sarcomas are increasingly being defined by molecular signatures and biological characteristics rather than by simple histopathology. Our group is translating this research on the basic biology of sarcomas into new therapeutics directed at novel targets.
The foremost example of our team's work has been the development of tyrosine kinase inhibitors as effective therapies for patients with gastrointestinal stromal tumor (GIST). By targeting the specific molecular signals of GIST, we have validated the concept that a human solid tumor can be treated by signal transduction inhibitors. This work led to the development and FDA approval of imatinib mesylate (Gleevec) as an effective therapy for patients with metastatic or unresectable GIST, and underlies our ongoing research in other novel agents, such as the kinase inhibitor SU11248.
Another example of molecular targeting of sarcomas in drug development is our pioneering interest in differentiation therapy for patients with liposarcomas. This research targets a nuclear receptor known as PPAR-gamma, which plays a role in the normal development of fat cells, and induces differentiation in liposarcomas to decrease proliferation. Larger studies based on our pilot data are now being designed to test the clinical value of this treatment, which we are refining with newer agents and methods.
Our group also is developing other agents against sarcomas, such as the natural product known as ET-743, derived from a marine organism. This drug, which binds to the DNA minor groove, has shown important clinical activity against several subtypes of sarcomas both in the laboratory and in extensive clinical trials. We are optimizing the dosage for this agent and moving forward in collaboration with other cancer centers to test the worth of this new drug.
Our multidisciplinary research team, including dedicated representatives from surgical oncology, radiation oncology, pathology, and other clinical arenas, works closely with laboratory investigators so that we can offer promising treatments of scientific merit to patients with sarcomas of soft tissue and bone.
- Oliveira AM, Perez-Atayde AR, Dal Cin P, Gebhart MC, Chen CJ, Neff JR, Demetri GD, Rosenberg AE, Bridge JA, Fletcher JA. Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes. Oncogene 2005;24:3419-26.
- Li FP, Fletcher JA, Heinrich MC, Garber JE, Sallan SE, Curiel-Lewandrowski C, Duensing A, van de Rijn M, Schnipper LE, Demetri GD. Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred. J Clin Oncol 2005;23:2735-43.
- Davis DW, Takamori R, Raut CP, Xiong HQ, Herbst RS, Stadler WM, Heymach JV, Demetri GD, Rashid A, Shen Y, Wen S, Abbruzzese JL McConkey DJ. Pharmacodynamic analysis of targeted inhibition and endothelial cell death in tumors treated with the vascular endothelial growth factor receptor antagonists SU5416 or SU6668. Clin Cancer Res 2005;11:6678-89.
- Garcia-Carbonero R, Supko JG, Maki RG, Manola J, Ryan DP, Harmon D, Puchalski TA, Goss G, Seiden MV, Waxman A, Quigley MT, Lopez T, Sancho MA, Jimeno J, Guzman C, Demetri GD. Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study. J Clin Oncol 2005;23:484-92.
- Grobmyer SR, Maki RG, Demetri GD, Mazumdar M, Riedel E, Brennan MF, Singer S. Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol 2004;15:1667-72.
- Nikolaidis P, Silverman SG, Cibas ES, Vansonnenberg E, Rybicki FJ, Manola JB, Tuncali K, Karshbaum SH, Singer S, Fletcher CD, Demetri GD. Liposarcoma subtypes: identification with computed tomography and ultrasound-guided percutaneous needle biopsy. Eur Radiol 2005;15:383-9.
- McArthur GA, Demetri GD, van Oosterom A, Heinrich MC, Debiec-Rychter M, Corless CL, Nikolova Z, Dimitrijevic S, Fletcher JA. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: imatinib target exploration consortium study B2225. J Clin Oncol 2005;23:866-73.
- Duensing A, Joseph NE, Medeiros F, Smith F, Hornick JL, Heinrich MC, Corless CL, Demetri GD, Fletcher CD, Fletcher JA. Protein kinase C theta (PKCtheta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs). Cancer Res 2004;64:5127-31.
- Heymach JV, Desai J, Manola J, Davis DW, McConkey DJ, Harmon D, Ryan DP, Goss G, Quigley T, Van den Abbeele AD, Silverman SG, Connors S, Folkman J, Fletcher CDM, Demetri GD. Phase II study of the antiangiogenic agent SU5416 in patients with advanced soft tissue sarcomas. Clin Cancer Res 2004;10:5732-40.
- Skankar S, vanSonnenberg E, Desai J, Dipiro PJ, Van Den Abbeele A, Demetri GD. Gastrointestinal stromal tumor: new nodule-within-a-mass pattern of recurrence after partial response to imatinib mesylate. Radiology 2005;235:892-8.
- George, Suzanne, MD
- Morgan, Jeffrey A., MD