Pemetrexed and Gemcitabine as Combination Therapy for the Treatment of Group3 Medulloblastoma
Menée in vitro et l'aide d'un modèle murin, cette étude suggère l'intérêt d'une combinaison pemetrexed-gemcitabine pour le traitement d'un sous-type de médulloblastome
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. "Group3 medulloblastoma neurospheres were screened with FDA-approved drugs "Pemetrexed and gemcitabine inhibited mouse and human G3 and mouse SHH MBs in vitro "Pemetrexed and gemcitabine increased survival of mice bearing mouse and human G3 MB "Pemetrexed and gemcitabine did not affect survival of mice bearing mouse SHH MB