[
  {"id":"boeckman_cisplatin_2005","abstract":"The combination of cisplatin and ionizing radiation treatment represents a common modality for treating a variety of cancers. These two agents provide considerable synergy during treatment although the mechanism of this synergy remains largely undefined. We have investigated the mechanism of cisplatin sensitization to IR using a combination of in vitro and in vivo experiments. A clear synergistic interaction between cisplatin and ionizing radiation (IR) is observed in cells proficient in non-homologous end joining (NHEJ) catalyzed repair of DNA double-strand breaks (DSB). In contrast, no interaction between cisplatin and IR is observed in NHEJ deficient cells. Reconstituted in vitro NHEJ assays revealed that a site-specific cisplatin-DNA lesion near the terminus results in complete abrogation of NHEJ catalyzed repair of the DSB. These data demonstrate that the cisplatin-IR synergistic interaction requires the DNA-PK dependent NHEJ pathway for joining of DNA DSBs, and the presence of a cisplatin lesion on the DNA blocks this pathway. In the absence of a functional NHEJ pathway, while the cells are hypersensitive to IR, there is no synergistic interaction with cisplatin.","accessed":{"date-parts":[[2020,7,4]]},"author":[{"family":"Boeckman","given":"Heather J."},{"family":"Trego","given":"Kelly S."},{"family":"Henkels","given":"Karen M."},{"family":"Turchi","given":"John J."}],"container-title":"Molecular cancer research : MCR","container-title-short":"Mol Cancer Res","DOI":"10.1158/1541-7786.MCR-04-0032","ISSN":"1541-7786","issue":"5","issued":{"date-parts":[[2005,5]]},"page":"277-285","PMCID":"PMC2432110","PMID":"15886299","source":"PubMed Central","title":"Cisplatin sensitizes cancer cells to ionizing radiation via inhibition of non-homologous end joining","type":"article-journal","URL":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2432110/","volume":"3"}
]