Research ArticleMedulloblastoma

Small-molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma

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Science Translational Medicine  20 Jan 2021:
Vol. 13, Issue 577, eaba7401
DOI: 10.1126/scitranslmed.aba7401

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Combined treatment for medulloblastoma

Certain subtypes of medulloblastoma (MB) have poor treatment outcome. To identify better treatments, Endersby et al. now screened more than 3000 compounds using six different human MB cell lines and showed that inhibitors of cell cycle checkpoint kinases (CHK1/2) increased the efficacy of clinical treatments. In vivo, the combined treatment increased DNA damage and apoptosis, resulting in increased survival and reduced tumor volume in multiple models. The results suggest that CHK1/2 inhibition could be used to increase the efficacy of standard chemotherapeutics for treating MB.

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