A Whole-Genome CRISPR Screen Identifies AHR Loss as a Mechanism of Resistance to a PARP7 Inhibitor.
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
05 07 2022
05 07 2022
Historique:
received:
12
10
2021
revised:
09
02
2022
accepted:
12
04
2022
pubmed:
20
4
2022
medline:
7
7
2022
entrez:
19
4
2022
Statut:
ppublish
Résumé
Inhibitors directed toward PARP1 and PARP2 are approved agents for the treatment of BRCA1 and BRCA2-related cancers. Other members of the PARP family have also been implicated in cancer and are being assessed as therapeutic targets in cancer and other diseases. Recently, an inhibitor of PARP7 (RBN-2397) has reached early-stage human clinical trials. Here, we performed a genome-wide CRISPR screen for genes that modify the response of cells to RBN-2397. We identify the polycyclic aromatic hydrocarbon receptor AHR and multiple components of the cohesin complex as determinants of resistance to this agent. Activators and inhibitors of AHR modulate the cellular response to PARP7 inhibition, suggesting potential combination therapy approaches.
Identifiants
pubmed: 35439318
pii: 694514
doi: 10.1158/1535-7163.MCT-21-0841
pmc: PMC9769698
mid: NIHMS1800357
doi:
Substances chimiques
Poly(ADP-ribose) Polymerase Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1076-1089Subventions
Organisme : NCI NIH HHS
ID : U54 CA209891
Pays : United States
Informations de copyright
©2022 American Association for Cancer Research.
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