RG7112, a Small-Molecule Inhibitor of MDM2, Enhances Trabectedin Response in Soft Tissue Sarcomas

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 inhib...

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Published in:Cancer investigation 2015-10, Vol.33 (9), p.440-450
Main Authors: 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
Format: Article
Language:English
Subjects:
Liposarcoma
MDM2
RG7112
Soft tissue sarcomas
Trabectedin
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Summary: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.
ISSN:0735-7907
1532-4192
DOI:10.3109/07357907.2015.1064534