Yondelis para el Tratamiento de Sarcomas Podría Aumentar y Mejorar su Respuesta Terapeutica ... RG7112, a Small-Molecule Inhibitor of MDM2, Enhances Trabectedin Response in Soft Tissue Sarcomas.

Published online: 14 Aug 2015 .

Obrador-Hevia A1, Martinez-Font E, Felipe-Abrio I, Calabuig-Fariñas S, Serra-Sitjar M, López-Guerrero JA, Ramos R, Alemany R, Martín-Broto J. .

Author information :

Group of Advanced Therapies and Biomarkers in Clinical Oncology, Institut d'Investigació Sanitària de Palma (IdISPa) , Palma de Mallorca , Spain.

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.