Pemetrexed and gemcitabine as combination therapy for the treatment of group3 medulloblastoma

Marie Morfouace, Anang Shelat, Megan Jacus, Burgess B. Freeman, David Turner, Sarah Robinson, Frederique Zindy, Yong Dong Wang, David Finkelstein, Olivier Ayrault, Laure Bihannic, Stephanie Puget, Xiao Nan Li, James M. Olson, Giles W. Robinson, R. Kiplin Guy, Clinton F. Stewart, Amar Gajjar, Martine F. Roussel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

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 invitro compared to control neurospheres and substantially inhibited G3 MB proliferation invivo. 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.

Original languageEnglish (US)
Pages (from-to)516-529
Number of pages14
JournalCancer Cell
Volume25
Issue number4
DOIs
StatePublished - Apr 14 2014

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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