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 Vol. 33; no. 9; pp. 440 - 450 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Informa Healthcare
21.10.2015
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Subjects | |
Online Access | Get full text |
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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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0735-7907 1532-4192 |
DOI: | 10.3109/07357907.2015.1064534 |