Literature DB >> 26288114

RG7112, a small-molecule inhibitor of MDM2, enhances trabectedin response in soft tissue sarcomas.

Antònia Obrador-Hevia1,2, Esther Martinez-Font1, Irene Felipe-Abrio3, Silvia Calabuig-Fariñas4, Margalida Serra-Sitjar5, José Antonio López-Guerrero6, Rafael Ramos7, Regina Alemany1,8, Javier Martín-Broto3,9.   

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.

Entities:  

Keywords:  Liposarcoma; MDM2; RG7112; Soft tissue sarcomas; Trabectedin

Mesh：

Substances：

Year:  2015        PMID： 26288114     DOI： 10.3109/07357907.2015.1064534

Source DB:  PubMed          Journal:  Cancer Invest        ISSN： 0735-7907            Impact factor:   2.176


  6 in total

1.  The MDM2 inducible promoter folds into four-tetrad antiparallel G-quadruplexes targetable to fight malignant liposarcoma.

Authors:  Sara Lago; Matteo Nadai; Emanuela Ruggiero; Martina Tassinari; Maja Marušič; Beatrice Tosoni; Ilaria Frasson; Filippo M Cernilogar; Valentina Pirota; Filippo Doria; Janez Plavec; Gunnar Schotta; Sara N Richter
Journal:  Nucleic Acids Res       Date:  2021-01-25       Impact factor: 16.971

Review 2.  TP53 in bone and soft tissue sarcomas.

Authors:  Elizabeth Thoenen; Amanda Curl; Tomoo Iwakuma
Journal:  Pharmacol Ther       Date:  2019-07-02       Impact factor: 12.310

3.  Activity of trabectedin and the PARP inhibitor rucaparib in soft-tissue sarcomas.

Authors:  Audrey Laroche; Vanessa Chaire; François Le Loarer; Marie-Paule Algéo; Christophe Rey; Kevin Tran; Carlo Lucchesi; Antoine Italiano
Journal:  J Hematol Oncol       Date:  2017-04-11       Impact factor: 17.388

Review 4.  MDM2 Amplified Sarcomas: A Literature Review.

Authors:  Raf Sciot
Journal:  Diagnostics (Basel)       Date:  2021-03-11

5.  CDK4 inhibition diminishes p53 activation by MDM2 antagonists.

Authors:  Anusha Sriraman; Antje Dickmanns; Zeynab Najafova; Steven A Johnsen; Matthias Dobbelstein
Journal:  Cell Death Dis       Date:  2018-09-11       Impact factor: 8.469

6.  Phase I study of daily and weekly regimens of the orally administered MDM2 antagonist idasanutlin in patients with advanced tumors.

Authors:  Antoine Italiano; Wilson H Miller; Jean-Yves Blay; Jourik A Gietema; Yung-Jue Bang; Linda R Mileshkin; Hal W Hirte; Brian Higgins; Steven Blotner; Gwen L Nichols; Lin Chi Chen; Claire Petry; Qi Joy Yang; Christophe Schmitt; Candice Jamois; Lillian L Siu
Journal:  Invest New Drugs       Date:  2021-06-28       Impact factor: 3.850
  6 in total

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