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MetabolomicsTargeting SLC1A5-mediated glutamine metabolism overcomes PARP inhibitor resistance in ovarian cancer

Poly(ADP-ribose) polymerase inhibitors (PARPi), such as olaparib, have significantly improved outcomes in ovarian cancer (OC); however, therapy resistance remains a major clinical challenge. Here, we showed that glutamine metabolism was upregulated in PARPi-resistant OC cells and identified the g...

2026-04-08 | MTBLS14072 | MetaboLights
ProteomicsHotspot SF3B1 mutations determine response to PARP inhibitors
Hotspot mutations in the spliceosomal component gene SF3B1 underpin a number of cancers and have a neomorphic function leading to global disruption of canonical splicing and aberrant splicing of hundreds of transcripts. However, the functional consequences of this misplicing and resultant genetic vu...
ORGANISM(S): Homo sapiens (Human) 
2023-04-19 | PXD019046 | Pride
Human Sf3b1 Ms3 Tmt Cancer Parp inhibitors 
ProteomicsA HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant
Although PARP inhibitors (PARPi) now form part of the standard-of-care for the treatment of homologous recombination defective cancers, de novo and acquired resistance limits their overall effectiveness. Previously, overexpression of the BRCA1-∆11q splice variant has been shown to cause PARPi resist...
ORGANISM(S): Homo sapiens (Human) 
2023-07-18 | PXD040430 | Pride
Brca1 Ovarian cancer Parp Huwe1 Parpi 
GenomicsMitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors
Mitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors
PRJNA1169552 | ENA
ProteomicsPARP Inhibitor Sensitivity in BRCA-Proficient ovarian cancer cells is regulated by the MSH6–CHAF1A axis: 2. ADP-Ribosylation
Ovarian cancer is the leading cause of gynecologic cancer-related deaths, with high-grade serous ovarian cancer (HGSOC) being the most common and lethal subtype. While BRCA1/2 mutations are established biomarkers predicting sensitivity to PARP inhibitors (PARPis), a subset of patients with BRCA-prof...
ORGANISM(S): Homo sapiens (Human) 
2026-08-21 | PXD067891 | Pride
Ovarian cancer Parp inhibitor Adp-ribosylation 
TranscriptomicsMitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors
PARP inhibitors (PARPis), known to elicit mitochondrial protection in non-oncological diseases by elevating the cellular NAD+ pool, exhibit potent cytotoxicity in selected human cancers. The role of mitochondrial metabolism in PARPi-mediated anti-tumor therapy remains unexplored. Here, we propose a ...
ORGANISM(S): Homo sapiens 
2026-09-06 | GSE278908 | GEO
GenomicsMitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors [ChIP-seq]
Mitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors [ChIP-seq]
PRJNA1169550 | ENA
GenomicsA genome-wide CRISPR screen identifies ZNF251 critical for resistance to PARP inhibitors
A genome-wide CRISPR screen identifies ZNF251 critical for resistance to PARP inhibitors
PRJNA844108 | ENA
OtherA genome-wide CRISPR screen identifies ZNF251 critical for resistance to PARP inhibitors
The poly (ADP-ribose) polymerases (PARPs) inhibitors are an exciting new class of agents that have shown efficacy in treating various cancers, especially these harboring BRCA1/2 mutations. The cancer associated BRCA1/2 mutations disrupt DNA double strand break (DSB) repair by homologous recombinatio...
ORGANISM(S): Homo sapiens 
2023-05-31 | GSE205221 | GEO
ProteomicsNASP modulates histone turnover to drive PARP inhibitor resistance
PARP inhibitors (PARPi) present a remarkable advance in the treatment of patients with homologous recombination (HR)-deficient tumors1-3, however resistance remains a challenge due to genomic instability4,5. While most research has focused on the downstream consequences of PARPi exposure to tackle r...
ORGANISM(S): Homo sapiens (Human) 
2025-07-29 | PXD061071 | Pride
Lc-msms Nasp Parp inhibitor Human 
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