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.

Public Health Relevance

While soft tissue sarcomas can be treated surgically, for advanced disease there are few effective systemic therapies. By discovering the molecular alterations that drive the formation and growth of sarcomas, we have an opportunity to identify new types of therapy for these deadly diseases. Insight into the molecular alterations will also allow for improved molecular subtyping and more precise prediction of tumor behavior.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
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Special Emphasis Panel (ZCA1-GRB-I (M1))
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Ujhazy, Peter
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Sloan-Kettering Institute for Cancer Research
New York
United States
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Tap, William D; Jones, Robin L; Van Tine, Brian A et al. (2016) Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet 388:488-97
Argani, Pedram; Reuter, Victor E; Zhang, Lei et al. (2016) TFEB-amplified Renal Cell Carcinomas: An Aggressive Molecular Subset Demonstrating Variable Melanocytic Marker Expression and Morphologic Heterogeneity. Am J Surg Pathol 40:1484-1495
Specht, Katja; Zhang, Lei; Sung, Yun-Shao et al. (2016) Novel BCOR-MAML3 and ZC3H7B-BCOR Gene Fusions in Undifferentiated Small Blue Round Cell Sarcomas. Am J Surg Pathol 40:433-42
Kao, Yu-Chien; Sung, Yun-Shao; Zhang, Lei et al. (2016) BCOR Overexpression Is a Highly Sensitive Marker in Round Cell Sarcomas With BCOR Genetic Abnormalities. Am J Surg Pathol 40:1670-1678
McFadden, David G; Politi, Katerina; Bhutkar, Arjun et al. (2016) Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma. Proc Natl Acad Sci U S A 113:E6409-E6417
Patwardhan, Parag P; Ivy, Kathryn S; Musi, Elgilda et al. (2016) Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. Oncotarget 7:4093-109
Leduc, Charles; Zhang, Lei; Öz, Buge et al. (2016) Thoracic Myoepithelial Tumors: A Pathologic and Molecular Study of 8 Cases With Review of the Literature. Am J Surg Pathol 40:212-23
Kao, Yu-Chien; Sung, Yun-Shao; Zhang, Lei et al. (2016) Recurrent BCOR Internal Tandem Duplication and YWHAE-NUTM2B Fusions in Soft Tissue Undifferentiated Round Cell Sarcoma of Infancy: Overlapping Genetic Features With Clear Cell Sarcoma of Kidney. Am J Surg Pathol 40:1009-20
Moore, Amanda R; Ceraudo, Emilie; Sher, Jessica J et al. (2016) Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma. Nat Genet 48:675-80
Huang, Shih-Chiang; Alaggio, Rita; Sung, Yun-Shao et al. (2016) Frequent HRAS Mutations in Malignant Ectomesenchymoma: Overlapping Genetic Abnormalities With Embryonal Rhabdomyosarcoma. Am J Surg Pathol 40:876-85

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