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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Cell Line, Tumor
  • Cerebellar Neoplasms / drug therapy*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Glutamates / administration & dosage
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives
  • High-Throughput Screening Assays
  • Humans
  • Medulloblastoma / drug therapy*
  • Mice
  • Mice, Transgenic
  • Pemetrexed
  • Prognosis

Substances

  • Glutamates
  • Pemetrexed
  • Deoxycytidine
  • Guanine
  • gemcitabine

Associated data

  • GEO/GSE46406