Pemetrexed and Gemcitabine as Combination Therapy for the Treatment of Group3 Medulloblastoma

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• 作者：Marie Morfouace¹ ; Anang Shelat² ; Megan Jacus³ ; Burgess B. Freeman III⁴ ; David Turner³ ; Sarah Robinson¹ ; Frederique Zindy¹ ; Yong-Dong Wang⁵ ; David Finkelstein⁵ ; Olivier Ayrault⁶ ; Laure Bihannic⁶ ; Stephanie Puget⁷ ; Xiao-Nan Li⁸ ; James M. Olson⁹ ; Giles W. Robinson¹⁰ ; R. Kiplin Guy² ; Clinton F. Stewart³ ; Amar Gajjar¹⁰ ; Martine F. Roussel¹ ; ^{martine.roussel@stjude.org" class="auth_mail}
• 刊名：Cancer Cell
• 出版年：14 April, 2014
• 年：2014
• 卷：25
• 期：4
• 页码：516-529
• 全文大小：2822 K

文摘

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Summary

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聽vitro compared to control neurospheres and substantially inhibited G3 MB proliferation in聽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.