Richard G. Gorlick, M.D.
My clinical interests are focused upon the care of children, adolescents and young adults afflicted with sarcomas. Our laboratory is interested in specific pediatric malignancies including osteosarcoma and leukemia. In the context of these malignancies we study drug resistance, potential therapeutic targets and mechanisms of pathogenesis with the aim being the improved treatment of these diseases. The longstanding focus of the laboratory has been the mechanisms of antifolate resistance that are observed in osteosarcoma and leukemia patient samples. These studies have led to further studies of the reduced folate carrier, the major protein transporter of folates and antifolates, intracellularly and the folate receptor an alternative transport route.
At present we are attempting to define the contribution of alterations in folate receptor and downstream antifolate polyglutamylation in resistance to these drugs. Other areas of interest include defining the signal transduction pathways relevant to osteosarcoma and to identify key genes involved in osteosarcoma pathogenesis. Comprehensive expression profiling using Serial Analysis of Gene Expression and oligonucleotide expression arrays of osteosarcoma subsets, osteoblasts and mesenchymal stem cells is being performed to address cell of origin questions as well as to identify critical genes in pathogenesis. Current interest exists in parthyroid hormone related peptide signaling pathways. A wide variety of functional and molecular approaches are used to study candidate genes as well as to address the drug resistance questions.
Huang HY, Illei PB, Zhao Z, Mazumdar M, Huvos AG, Healey JH, Wexler LH, Gorlick R, Meyers P, Ladanyi M. Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: A highly lethal subset associated with poor chemoresponse. J Clin Oncol 2005; 23:548-558.
Mintz MB, Sowers R, Brown KM, Hilmer SC, Mazza B, Huvos AG, Meyers PA, LaFleur B, McDonough WS, Henry MM, Ramsey KE, Antonescu CR, Chen W, Healey JH, Daluski A, Berens ME, MacDonald TJ, Gorlick R, Stephan DA. An expression signature classifies chemotherapy-resistant pediatric osteosarcoma. Cancer Res 2005; 65:1748-1754.
Zelcer S, Kellick M, Wexler LH, Shi W, Sankaran M, Lo S, Healey J, Huvos AG, Meyers PA, Gorlick R. Methotrexate levels and outcome in osteosarcoma. Ped Blood Cancer 2005; 44:638-642.
Spees WM, Gade TP, Yang G, Tong WP, Bornmann WG, Gorlick R, Koutcher JA. An 19F magnetic resonance-based in vivo assay of solid tumor methotrexate resistance: Proof of principle. Clin Cancer Res 2005; 11:1454-1461
Nathan SS, DiResta GR, Casas-Ganem JE, Hoang BH, Sowers R, Yang R, Huvos AG, Gorlick R, Healey JH. Elevated physiological tumor pressure promotes proliferation and chemosensitivity in human osteosarcoma. Clin Cancer Res 2005; 11:2389-2397.
Laverdiere C, Hoang BH, Yang R, Sowers R, Qin J, Meyers PA, Huvos AG, Healey JH, Gorlick R mRNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma. Clin Cancer Res 2005; 11:2561-2567.
Diresta GR, Nathan SS, Manoso MW, Casas-Ganem J, Wyatt C, Kubo T, Boland PJ, Athanasian EA, Miodownik J, Gorlick R, Healey JH. Cell proliferation of cultured human cancer cells are affected by the elevated tumor pressures that exist in vivo. Ann Biomed Eng 2005:33:1270-1280.
Chou AJ, Merola PR, Wexler LH, Gorlick RG, Vyas YM, Healey JH, Laquaglia MP, Huvos AG, Meyers PA. Treatment of osteosarcoma at first recurrence after contemporary therapy. Cancer 2005;104:2214-2221.
Cheung NK, Sowers R, Vickers AJ, Cheung IY, Kushner BH, Gorlick R. FCGR2A polymorphism is correlated with clinical outcome following immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony stimulating factor. J Clin Oncol, 2006;24:2885-2890.
Nathan SS, Gorlick R, Bukata S, Chou A, Morris CD, Boland PJ, Huvos AG, Meyers PA, Healey JH. Treatment algorithm for locally recurrent osteosarcoma based on local disease free interval and the presence of lung metastasis. Cancer 2006;107:1607-1616.
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