Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer.
Antineoplastic Agents
/ pharmacology
Apoptosis
/ genetics
Apoptosis Regulatory Proteins
/ genetics
Cell Line, Tumor
Cisplatin
/ pharmacology
Drug Resistance, Neoplasm
Female
Genomics
Humans
Myeloid Cell Leukemia Sequence 1 Protein
/ antagonists & inhibitors
Ovarian Neoplasms
/ drug therapy
Paclitaxel
/ pharmacology
bcl-X Protein
/ antagonists & inhibitors
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
20
11
2018
revised:
07
04
2019
accepted:
22
08
2019
pubmed:
30
8
2019
medline:
29
7
2020
entrez:
30
8
2019
Statut:
ppublish
Résumé
High-grade serous ovarian cancer (HGSOC) is often sensitive to initial treatment with platinum and taxane combination chemotherapy, but most patients relapse with chemotherapy-resistant disease. To systematically identify genes modulating chemotherapy response, we performed pooled functional genomic screens in HGSOC cell lines treated with cisplatin, paclitaxel, or cisplatin plus paclitaxel. Genes in the intrinsic pathway of apoptosis were among the top candidate resistance genes in both gain-of-function and loss-of-function screens. In an open reading frame overexpression screen, followed by a mini-pool secondary screen, anti-apoptotic genes including
Identifiants
pubmed: 31462500
pii: 1541-7786.MCR-18-1243
doi: 10.1158/1541-7786.MCR-18-1243
pmc: PMC6825578
mid: NIHMS1538529
doi:
Substances chimiques
Antineoplastic Agents
0
Apoptosis Regulatory Proteins
0
BCL2L1 protein, human
0
MCL1 protein, human
0
Myeloid Cell Leukemia Sequence 1 Protein
0
bcl-X Protein
0
Paclitaxel
P88XT4IS4D
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2281-2293Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR001100
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA222554
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA237871
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197568
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224068
Pays : United States
Organisme : NCI NIH HHS
ID : K99 CA222554
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA180733
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA219943
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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