The long-term goal of the SPORE in Soft Tissue Sarcoma is to reduce morbidity and mortality from soft tissue sarcoma by developing therapies targeted to the molecular, genetic, epigenetic, and signaling pathway alterations that are specific to sarcoma type and subtype. To pursue this, we will focus our efforts on 3 broad translational research objectives: 1. Define shared and type-specific molecular mechanisms of sarcomagenesis to identify new rational therapeutic targets, 2. Define mechanisms of resistance to targeted therapies, 3. Develop and validate targeted therapies in clinical studies. To achieve these goals we have marshaled an integrated, multidisciplinary group of basic and clinical investigators all armed with a unique resource, a clinicopathologic and outcomes database prospectively collected over a 27-year period containing data for over 8300 patients treated for soft tissue sarcoma at MSKCC. This database has been linked for the past 16 years to an institutional tissue bank, and for the past 7 years to a comprehensive tissue procurement process for establishment of primary sarcoma cell lines and mouse xenograft models of human sarcoma. The SPORE is structured around 4 research projects, 3 cores, and career development and developmental research programs. Each research project focuses on at least one of the 3 broad translational research goals listed above. RP-1 (Imatinib Resistance) aims to identify new therapeutic targets and develop new treatment strategies for pediatric and imatinib-resistant GIST. RP-2 (PDGFR/PI3K/mT0R Targeting) evaluates strategies for targeting PDGFRA signaling and reducing activated Akt in synovial sarcoma and sarcoma types that show increased expression of PDGFRA using cell lines, xenograft models, and phase II clinical trials. RP-3 (Target Discovery) aims to identify genomic drivers of oncogenesis in myxofibrosarcoma and pleomorphic malignant fibrous histiocytoma so as to identify new therapeutic targets. RP-4 (Epigenetic Therapy) aims to elucidate the epigenetic mechanisms and histone code alterations involved in the deregulation of SYT-SSX target genes in synovial sarcoma so as to enhance our understanding of synovial sarcoma pathogenesis and guide the development of new selective epigenetic therapies.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-I (M1))
Program Officer
Ujhazy, Peter
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Sloan-Kettering Institute for Cancer Research
New York
United States
Zip Code
Agaram, Narasimhan P; Chen, Chun-Liang; Zhang, Lei et al. (2014) Recurrent MYOD1 mutations in pediatric and adult sclerosing and spindle cell rhabdomyosarcomas: evidence for a common pathogenesis. Genes Chromosomes Cancer 53:779-87
Antonescu, Cristina R; Chen, Hsiao-Wei; Zhang, Lei et al. (2014) ZFP36-FOSB fusion defines a subset of epithelioid hemangioma with atypical features. Genes Chromosomes Cancer 53:951-9
Kohsaka, Shinji; Shukla, Neerav; Ameur, Nabahet et al. (2014) A recurrent neomorphic mutation in MYOD1 defines a clinically aggressive subset of embryonal rhabdomyosarcoma associated with PI3K-AKT pathway mutations. Nat Genet 46:595-600
Kim, Teresa S; Cavnar, Michael J; Cohen, Noah A et al. (2014) Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal stromal tumor. Clin Cancer Res 20:2350-62
Qin, Li-Xuan; Breeden, Linda; Self, Steven G (2014) Finding gene clusters for a replicated time course study. BMC Res Notes 7:60
Brennan, Murray F; Antonescu, Cristina R; Moraco, Nicole et al. (2014) Lessons learned from the study of 10,000 patients with soft tissue sarcoma. Ann Surg 260:416-21; discussion 421-2
Patwardhan, Parag P; Surriga, Oliver; Beckman, Michael J et al. (2014) Sustained inhibition of receptor tyrosine kinases and macrophage depletion by PLX3397 and rapamycin as a potential new approach for the treatment of MPNSTs. Clin Cancer Res 20:3146-58
Weinreb, Ilan; Zhang, Lei; Tirunagari, Laxmi M S et al. (2014) Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin. Genes Chromosomes Cancer 53:845-56
Antonescu, Cristina R; Sung, Yun-Shao; Chen, Chun-Liang et al. (2014) Novel ZC3H7B-BCOR, MEAF6-PHF1, and EPC1-PHF1 fusions in ossifying fibromyxoid tumors--molecular characterization shows genetic overlap with endometrial stromal sarcoma. Genes Chromosomes Cancer 53:183-93
Lee, William; Teckie, Sewit; Wiesner, Thomas et al. (2014) PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. Nat Genet 46:1227-32

Showing the most recent 10 out of 37 publications