Functionally defined therapeutic targets in diffuse intrinsic pontine glioma

Catherine S. Grasso, Yujie Tang, Nathalene Truffaux, Noah E. Berlow, Lining Liu, Marie Anne Debily, Michael J. Quist, Lara E. Davis, Elaine C. Huang, Pamelyn J. Woo, Anitha Ponnuswami, Spenser Chen, Tessa B. Johung, Wenchao Sun, Mari Kogiso, Yuchen Du, Lin Qi, Yulun Huang, Marianne Hütt-Cabezas, Katherine E. WarrenLudivine Le Dret, Paul S. Meltzer, Hua Mao, Martha Quezado, Dannis G. Van Vuurden, Jinu Abraham, Maryam Fouladi, Matthew N. Svalina, Nicholas Wang, Cynthia Hawkins, Javad Nazarian, Marta M. Alonso, Eric H. Raabe, Esther Hulleman, Paul T. Spellman, Xiao Nan Li, Charles Keller, Ranadip Pal, Jacques Grill, Michelle Monje

Research output: Contribution to journalArticle

241 Scopus citations

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNA-seq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat demonstrated therapeutic efficacy both in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat and the histone demethylase inhibitor GSK-J4 revealed that the two had synergistic effects. Together, these data suggest a promising therapeutic strategy for DIPG.

Original languageEnglish
Pages (from-to)555-559
Number of pages5
JournalNature Medicine
Volume21
Issue number6
DOIs
StatePublished - Jun 9 2015

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    Grasso, C. S., Tang, Y., Truffaux, N., Berlow, N. E., Liu, L., Debily, M. A., Quist, M. J., Davis, L. E., Huang, E. C., Woo, P. J., Ponnuswami, A., Chen, S., Johung, T. B., Sun, W., Kogiso, M., Du, Y., Qi, L., Huang, Y., Hütt-Cabezas, M., ... Monje, M. (2015). Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nature Medicine, 21(6), 555-559. https://doi.org/10.1038/nm.3855