Research ArticleCancer

Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51

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Science Translational Medicine  15 May 2019:
Vol. 11, Issue 492, eaav4508
DOI: 10.1126/scitranslmed.aav4508

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The secret life of cediranib

Anti-angiogenic agents are used to inhibit the formation of new blood vessels that supply nutrition and oxygen to tumors, but recent findings suggest that they can have additional anticancer effects. In particular, a clinical study unexpectedly found that the anti-angiogenic drug cediranib can sensitize tumors to poly(ADP-ribose) polymerase (PARP) inhibitors, which normally target tumors with defective DNA repair. Kaplan et al. determined that cediranib not only damages tumors by interrupting their blood supply and thereby inducing hypoxia but also directly affects pathways involved in DNA repair, sensitizing cancer cells to PARP inhibitors and suggesting a strategy for targeted treatment.