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RITA displays anti-tumor activity in medulloblastomas independent of TP53 status

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Item Type:Article
Title:RITA displays anti-tumor activity in medulloblastomas independent of TP53 status
Creators Name:Gottlieb, A. and Althoff, K. and Grunewald, L. and Thor, T. and Odersky, A. and Schulte, M. and Deubzer, H.E. and Heukamp, L. and Eggert, A. and Schramm, A. and Schulte, J.H. and Künkele, A.
Abstract:Current therapy of medulloblastoma, the most common malignant brain tumor of childhood, achieves 40-70% survival. Secondary chemotherapy resistance contributes to treatment failure, where TP53 pathway dysfunction plays a key role. MDM2 interaction with TP53 leads to its degradation. Reactivating TP53 functionality using small-molecule inhibitors, such as RITA, to disrupt TP53-MDM2 binding may have therapeutic potential. We show here that RITA decreased viability of all 4 analyzed medulloblastoma cell lines, regardless of TP53 functional status. The decrease in cell viability was accompanied in 3 of the 4 medulloblastoma cell lines by accumulation of TP53 protein in the cells and increased CDKN1A expression. RITA treatment in mouse models inhibited medulloblastoma xenograft tumor growth. These data demonstrate that RITA treatment reduces medulloblastoma cell viability in both in vitro and in vivo models, and acts independently of cellular TP53 status, identifying RITA as a potential therapeutic agent to treat medulloblastoma.
Keywords:RITA, Medulloblastoma, TP53, MDM2, CDKN1A, Animals, Mice
Publisher:Impact Journals
Page Range:27882-27891
Date:25 April 2017
Official Publication:https://doi.org/10.18632/oncotarget.15840
PubMed:View item in PubMed

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