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RG7112, a small-molecule inhibitor of MDM2, enhances trabectedin response in soft tissue sarcomas.
Obrador-Hevia, Antònia; Martinez-Font, Esther; Felipe-Abrio, Irene; Calabuig-Fariñas, Silvia; Serra-Sitjar, Margalida; López-Guerrero, José Antonio; Ramos, Rafael; Alemany, Regina; Martín-Broto, Javier.
Afiliação
  • Obrador-Hevia A; a 1 Group of Advanced Therapies and Biomarkers in Clinical Oncology , Institut d'Investigació Sanitària de Palma (IdISPa) , Palma de Mallorca, Spain.
  • Martinez-Font E; b 2 Department of Oncology , Hospital Universitari Son Espases, Palma de Mallorca , Spain.
  • Felipe-Abrio I; a 1 Group of Advanced Therapies and Biomarkers in Clinical Oncology , Institut d'Investigació Sanitària de Palma (IdISPa) , Palma de Mallorca, Spain.
  • Calabuig-Fariñas S; c 3 Group of Molecular Oncology and New Therapies, Oncohematology and Genetics Department , Instituto de Biomedicina de Sevilla (IBiS) , Sevilla, Spain.
  • Serra-Sitjar M; d 4 Molecular Oncology Laboratory, Fundación de Investigación , Hospital General Universitario de Valencia , Valencia, Spain.
  • López-Guerrero JA; e 5 Cancer Cell Biology Group, Institut Universitari d'Investigacions en Ciències de la Salut (IUNICS) , University of the Balearic Islands , Palma de Mallorca, Spain.
  • Ramos R; f 6 Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología , Valencia, Spain.
  • Alemany R; g 7 Department of Pathology , Hospital Universitari Son Espases , Palma de Mallorca, Spain.
  • Martín-Broto J; a 1 Group of Advanced Therapies and Biomarkers in Clinical Oncology , Institut d'Investigació Sanitària de Palma (IdISPa) , Palma de Mallorca, Spain.
Cancer Invest ; 33(9): 440-50, 2015.
Article em En | MEDLINE | ID: mdl-26288114
ABSTRACT
MDM2 is a critical negative regulator of the p53 tumor suppressor protein. Selected sarcoma subtypes are being treated with Trabectedin in second line, which promotes DNA damage and p53-dependent apoptosis. The aim of this study was to evaluate the improvement of Trabectedin response with MDM2 inhibitors in soft tissue sarcomas. The antitumor effects of Trabectedin, Nutlin-3A and RG7112 as single agents or in combination were examined in vitro. RG7112 significantly synergized with Trabectedin in MDM2-amplified liposarcoma cells, representing a promising new therapeutic strategy for the treatment of sarcomas with MDM2 amplification.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sarcoma / Tetra-Hidroisoquinolinas / Imidazolinas / Dioxóis / Proteínas Proto-Oncogênicas c-mdm2 / Antineoplásicos Limite: Humans Idioma: En Revista: Cancer Invest Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Espanha
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sarcoma / Tetra-Hidroisoquinolinas / Imidazolinas / Dioxóis / Proteínas Proto-Oncogênicas c-mdm2 / Antineoplásicos Limite: Humans Idioma: En Revista: Cancer Invest Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Espanha