Journal
CANCER INVESTIGATION
Volume 33, Issue 9, Pages 440-450Publisher
TAYLOR & FRANCIS INC
DOI: 10.3109/07357907.2015.1064534
Keywords
Soft tissue sarcomas; Trabectedin; RG7112; MDM2; Liposarcoma
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Funding
- Institute of Health Carlos III (Ministerio de Economia y Competitividad)
- EC (European Regional Development Fund [ERDF]) [PI12/01748]
- Pharamar
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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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