Identification of a Synthetic Lethal Relationship between Nucleotide Excision Repair Deficiency and Irofulven Sensitivity in Urothelial Cancer.
Judit BörcsökZsófia M SztupinszkiRaie BekeleSizhi P GaoMiklos DiossyAmruta S SamantKasia M DillonViktoria TiszaSándor SpisákOrsolya RuszIstvan CsabaiHelle PappotZoë J FrazierDavid J KonieczkowskiDavid R LiuNaresh VasaniJames A RodriguesDavid B SolitJean H Hoffman-CensitsElizabeth R PlimackJonathan E RosenbergJean-Bernard LazaroMary-Ellen TaplinGopa IyerSøren BrunakRita LozsaEliezer M Van AllenDávid SzütsKent W MouwZoltan SzallasiPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2020)
Tumor NER deficiency confers sensitivity to irofulven, a previously abandoned anticancer agent, with minimal activity in NER-proficient cells. A composite mutational signature of NER deficiency may be useful in identifying patients likely to respond to NER-targeting agents, including cisplatin and irofulven.See related commentary by Jiang and Greenberg, p. 1833.