BACKGROUND: Synovial sarcoma is a soft tissue malignancy with a predilection for adolescents and young adults. Despite recent improvements in the understanding of its character and etiology, few therapeutic advances have been made. The mortality rate is high among the young population it affects. The low incidence of most subtypes of sarcoma, such as synovial sarcoma, makes disease-specific trials difficult to organize. The biological differences between sarcoma subtypes make inclusion of multiple types in general trials unsatisfactory as well. METHODS: A review of the literature regarding targetable pathways in synovial sarcoma was undertaken. A strategy has been devised to utilize available technologies in order to prioritize drug trial planning. RESULTS: Cell culture and xenograft research with synovial sarcoma cell lines have identified some critical pathways that may be targetable. Promising therapeutic strategies include newer cytotoxic chemotherapies, antiangiogenic agents, anti-IGF1R pathway agents, anti-Bcl-2/proapoptotic agents, and histone deacetylase complex inhibitors. CONCLUSIONS: We propose to prioritize potential therapeutic strategies via preclinical testing of agents in a genetic mouse model of synovial sarcoma. Preclinical optimization of treatment regimens can guide the development of more focused patient trials.
BACKGROUND:Synovial sarcoma is a soft tissue malignancy with a predilection for adolescents and young adults. Despite recent improvements in the understanding of its character and etiology, few therapeutic advances have been made. The mortality rate is high among the young population it affects. The low incidence of most subtypes of sarcoma, such as synovial sarcoma, makes disease-specific trials difficult to organize. The biological differences between sarcoma subtypes make inclusion of multiple types in general trials unsatisfactory as well. METHODS: A review of the literature regarding targetable pathways in synovial sarcoma was undertaken. A strategy has been devised to utilize available technologies in order to prioritize drug trial planning. RESULTS: Cell culture and xenograft research with synovial sarcoma cell lines have identified some critical pathways that may be targetable. Promising therapeutic strategies include newer cytotoxic chemotherapies, antiangiogenic agents, anti-IGF1R pathway agents, anti-Bcl-2/proapoptotic agents, and histone deacetylase complex inhibitors. CONCLUSIONS: We propose to prioritize potential therapeutic strategies via preclinical testing of agents in a genetic mouse model of synovial sarcoma. Preclinical optimization of treatment regimens can guide the development of more focused patient trials.
Authors: T Mancuso; A Mezzelani; C Riva; A Fabbri; L Dal Bo; G Sampietro; P Perego; P Casali; F Zunino; G Sozzi; M A Pierotti; S Pilotti Journal: Lab Invest Date: 2000-06 Impact factor: 5.662
Authors: N Friedrichs; J Küchler; E Endl; A Koch; J Czerwitzki; P Wurst; D Metzger; J H Schulte; M I Holst; L C Heukamp; O Larsson; S Tanaka; A Kawai; E Wardelmann; R Buettner; T Pietsch; W Hartmann Journal: J Pathol Date: 2008-12 Impact factor: 7.996
Authors: Anna Minchom; Robin L Jones; Cyril Fisher; Omar Al-Muderis; Sue Ashley; Michelle Scurr; Vasilios Karavasilis; Ian R Judson Journal: Sarcoma Date: 2010-05-20
Authors: Paul A Meyers; Cindy L Schwartz; Mark D Krailo; John H Healey; Mark L Bernstein; Donna Betcher; William S Ferguson; Mark C Gebhardt; Allen M Goorin; Michael Harris; Eugenie Kleinerman; Michael P Link; Helen Nadel; Michael Nieder; Gene P Siegal; Michael A Weiner; Robert J Wells; Richard B Womer; Holcombe E Grier Journal: J Clin Oncol Date: 2008-02-01 Impact factor: 44.544
Authors: Stefan Sleijfer; Monia Ouali; Martine van Glabbeke; Anders Krarup-Hansen; Sjoerd Rodenhuis; Axel Le Cesne; Pancras C W Hogendoorn; Jaap Verweij; Jean-Yves Blay Journal: Eur J Cancer Date: 2010-01 Impact factor: 9.162
Authors: Joanna M Lubieniecka; Diederik R H de Bruijn; Le Su; Anke H A van Dijk; Subbaya Subramanian; Matt van de Rijn; Neal Poulin; Ad Geurts van Kessel; Torsten O Nielsen Journal: Cancer Res Date: 2008-06-01 Impact factor: 12.701
Authors: Livnat Jerby-Arnon; Cyril Neftel; Marni E Shore; Hannah R Weisman; Nathan D Mathewson; Matthew J McBride; Brian Haas; Benjamin Izar; Angela Volorio; Gaylor Boulay; Luisa Cironi; Alyssa R Richman; Liliane C Broye; Joseph M Gurski; Christina C Luo; Ravindra Mylvaganam; Lan Nguyen; Shaolin Mei; Johannes C Melms; Christophe Georgescu; Ofir Cohen; Jorge E Buendia-Buendia; Asa Segerstolpe; Malika Sud; Michael S Cuoco; Danny Labes; Simon Gritsch; Daniel R Zollinger; Nicole Ortogero; Joseph M Beechem; G Petur Nielsen; Ivan Chebib; Tu Nguyen-Ngoc; Michael Montemurro; Gregory M Cote; Edwin Choy; Igor Letovanec; Stéphane Cherix; Nikhil Wagle; Peter K Sorger; Alex B Haynes; John T Mullen; Ivan Stamenkovic; Miguel N Rivera; Cigall Kadoch; Kai W Wucherpfennig; Orit Rozenblatt-Rosen; Mario L Suvà; Nicolò Riggi; Aviv Regev Journal: Nat Med Date: 2021-01-25 Impact factor: 87.241