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Cancer Cell. 2014 Apr 14;25(4):516-29. doi: 10.1016/j.ccr.2014.02.009. Epub 2014 Mar 27.

Pemetrexed and gemcitabine as combination therapy for the treatment of Group3 medulloblastoma.

Author information

1
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
2
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
3
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
4
Department of Preclinical Pharmacokinetics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
5
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
6
Institut Curie/CNRS UMR 3306/INSERM U1005 Building 110, Centre Universitaire, 91405 Orsay, Cedex, France.
7
AP-HP, Department of Neurosurgery, Necker-Enfants Malades Hospital, Université Rene Descartes, 75015 Paris, France.
8
Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX 77030, USA.
9
Department of Pediatric Hematology-Oncology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
10
Department of NeuroOncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
11
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: martine.roussel@stjude.org.

Abstract

We devised a high-throughput, cell-based assay to identify compounds to treat Group3 medulloblastoma (G3 MB). Mouse G3 MBs neurospheres were screened against a library of approximately 7,000 compounds including US Food and Drug Administration-approved drugs. We found that pemetrexed and gemcitabine preferentially inhibited G3 MB proliferation in vitro compared to control neurospheres and substantially inhibited G3 MB proliferation in vivo. When combined, these two drugs significantly increased survival of mice bearing cortical implants of mouse and human G3 MBs that overexpress MYC compared to each agent alone, while having little effect on mouse MBs of the sonic hedgehog subgroup. Our findings strongly suggest that combination therapy with pemetrexed and gemcitabine is a promising treatment for G3 MBs.

PMID:
24684846
PMCID:
PMC3994669
DOI:
10.1016/j.ccr.2014.02.009
[Indexed for MEDLINE]
Free PMC Article
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