Targeting Germline- and Tumor-Associated Nucleotide Excision Repair Defects in Cancer.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
received:
21
08
2020
revised:
19
10
2020
accepted:
12
11
2020
pubmed:
18
11
2020
medline:
26
11
2021
entrez:
17
11
2020
Statut:
ppublish
Résumé
Nucleotide excision repair (NER) gene alterations constitute potential cancer therapeutic targets. We explored the prevalence of NER gene alterations across cancers and putative therapeutic strategies targeting these vulnerabilities. We interrogated our institutional dataset with mutational data from more than 40,000 patients with cancer to assess the frequency of putative deleterious alterations in four key NER genes. Gene-edited isogenic pairs of wild-type and mutant We found that putative damaging germline and somatic alterations in NER genes were present with frequencies up to 10% across multiple cancer types. Both These findings provide novel insights into a synthetic lethal relationship between clinically observed NER gene deficiencies and sensitivity to irofulven and its potential synergistic combination with other drugs.
Identifiants
pubmed: 33199492
pii: 1078-0432.CCR-20-3322
doi: 10.1158/1078-0432.CCR-20-3322
pmc: PMC8191507
mid: NIHMS1647990
doi:
Substances chimiques
Xeroderma Pigmentosum Group D Protein
EC 3.6.4.12
ERCC2 protein, human
EC 5.99.-
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Comment
Langues
eng
Sous-ensembles de citation
IM
Pagination
1997-2010Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221745
Pays : United States
Organisme : NIH HHS
ID : U54 OD020355
Pays : United States
Commentaires et corrections
Type : CommentOn
Informations de copyright
©2020 American Association for Cancer Research.
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