Sarcoma Research Group Group leader: Òscar Martínez Tirado

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1 Sarcoma Research Group Group leader: Òscar Martínez Tirado

2 IDIBELL since 2007 Miguel Servet program (Fondo de Investigaciones Sanitarias) 2009 Sarcoma Research Group (SGR682) Group leader: Òscar Martínez Tirado, PhD Pre-Doctoral Student: Miguel Sainz Jaspeado Pre-Doctoral Student: Laura Lagares Tena Master Student: Juan Huertas Martinez Clinical Coordinator: Xavier García del Muro Solans, MD, PhD Patologist: Xavier Sanjuán Garriga, MD MD/PhD Fellow: Juan Martín Liberal, MD

3 Research lines: -Biological role of caveolin-1 in sarcomas Funding: Mecanismos moleculares regulados por caveolina-1 durante la progresión tumoral del sarcoma de Ewing Funding Agency: ISCIII Regulación de la angiogénesis en el sarcoma de Ewing: papel de la caveolina-1 Funding Agency: ISCIII Estudio del proceso metastásico en la familia de tumores del sarcoma de Ewing: función biológica de la caveolina-1 Funding Agency: ISCIII Startup grant

4 -Biological role of caveolin-1 in sarcomas Ewing s sarcoma: We have demonstrated the involvement of this protein in the resistance to chemotherapy and their ability cells to metastasize. We are currently investigating its involvement in the regulation of blood supply and the possible mechanisms by which controls such processes (Dr Àngels Fabra from the Biological clues of the invasive and metastasic phenotype Group). Miguel Sáinz-Jaspeado, Laura Lagares-Tena, Jaime Lasheras, Fariba Navid, Carlos Rodriguez-Galindo, Silvia Mateo-Lozano, Vicente Notario, Xavier Sanjuan, Xavier Garcia del Muro, Àngels Fabra and Oscar M Tirado*. Caveolin-1 modulates the ability of Ewing s sarcoma to metastasize. Mol Cancer Res, 2010; In press. * Senior authorship. Impact factor 2008: Oscar M. Tirado, Caitlin M. MacCarthy, Naheed Fatima, Joaquin Villar, Silvia Mateo-Lozano and Vicente Notario. Caveolin-1 promotes resistance to chemotherapy-induced apoptosis in Ewing s sarcoma cells by modulating PKCα phosphorylation. Int, J. Cancer, 2010; 126(2): Impact factor 2008: 4.722

5 -Identification of new therapeutic targets and preclinical evaluation of new compounds for the treatment of sarcomas. Funding: FUS/CHOP as therapeutic target in Myxoid/Cell Round Liposarcoma. Sponsor: GEIS Sirolimus PI: Oscar Martinez Phase I/II clinical trial of the combination gemcitabine plus rapamycin vs gemcitabine alone in soft tissue sarcomas. Funding Agency: Ministerio de Sanidad y Política Social Sirolimus PI: Xavier García del Muro Phase I/II clinical trial to assess security and eficacy of Sorafenib (BAY ) and Iphosphamide combination in the treatment of soft tissue sarcoma patients Ongoing PI: Xavier García del Muro

6 -Identification of new therapeutic targets and preclinical evaluation of new compounds for the treatment of sarcomas. We are testing in vitro and in vivo several new compounds on soft tissue sarcoma cell lines to obtain preclinical data for future clinical trials. mtor inhibitors: We are currently testing mtorc1 and mtorc2 inhibitors on myxoid liposarcomas and Ewing s sarcomas and exploring the mechanisms by which they are effective. We are interested in dual PI3K/mTOR inhibitors and MEK inhibitors (everolimus +MEK162) CDK s inhibitors: We are currently testing these inhibitors in several soft tissue sarcomas. Glucose inhibitors for the treatment of rhabdomyosarcomas (Collaboration with Cristina Muñoz Pinedo from the Cell Death Regulation Group)

7 García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study J Clin Oncol. 2011; 29: Martin Liberal J, Martin J, Lopez-Pousa A, Cubedo R, Tirado OM and Garcia del Muro X. Phase I study of Sorafenib plus Iphosphamide in patients with advance sarcoma: a Spanish Group for research on sarcomas (GEIS) study. Br J Cancer. 2012; Submitted Maurel J, Martins AS, Poveda A, López-Guerrero JA, Cubedo R, Casado A, Martínez- Trufero J, Ramón Ayuso J, Lopez-Pousa A, Garcia-Albeniz X, Garcia del Muro X, de Alava E. Imatinib plus low-dose doxorubicin in patients with advanced gastrointestinal stromal tumors refractory to high-dose imatinib: a phase I-II study by the Spanish Group for Research on Sarcomas Cancer. 2010; 116:

8 Chromosomal translocation-associated sarcomas

9 Our interest: Targeting translocations Problem: Traditionaly undrugable targets Strategy: Nanotechnology?

10 Sarcoma Research Group Group leader: Òscar Martínez Tirado

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