Functionally-defined Therapeutic Targets in Diffuse Intrinsic Pontine Glioma: A Report of the Children’s Oncology Group DIPG Preclinical Consortium

Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNAseq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor pano...

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Detalles Bibliográficos
Autores principales: Grasso, Catherine S., Tang, Yujie, Truffaux, Nathalene, Berlow, Noah E., Liu, Lining, Debily, Marie-Anne, Quist, Michael J., Davis, Lara E., Huang, Elaine C., Woo, Pamelyn J, Ponnuswami, Anitha, Chen, Spenser, Johung, Tessa B., Sun, Wenchao, Kogiso, Mari, Du, Yuchen, Lin, Qi, Huang, Yulun, Hütt-Cabezas, Marianne, Warren, Katherine E., Dret, Ludivine Le, Meltzer, Paul S., Mao, Hua, Quezado, Martha, van Vuurden, Dannis G., Abraham, Jinu, Fouladi, Maryam, Svalina, Matthew N., Wang, Nicholas, Hawkins, Cynthia, Nazarian, Javad, Alonso, Marta M., Raabe, Eric, Hulleman, Esther, Spellman, Paul T., Li, Xiao-Nan, Keller, Charles, Pal, Ranadip, Grill, Jacques, Monje, Michelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862411/
https://www.ncbi.nlm.nih.gov/pubmed/25939062
http://dx.doi.org/10.1038/nm.3855
Descripción
Sumario:Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNAseq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat demonstrated efficacy in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat with histone demethylase inhibitor GSKJ4 revealed synergy. Together, these data suggest a promising therapeutic strategy for DIPG.

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