ArticleOncogene2023
A HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- Synthetic rescue in Saccharomyces cerevisiae: Concepts, large-scale genetic mapping, and functional implications.Journal of microbiology (Seoul, Korea) · 2026Review
- Targeting Replication Fork Processing Synergizes with PARP Inhibition to Potentiate Lethality in Homologous Recombination Proficient Ovarian Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- BRCA1 secondary splice-site mutations drive exon-skipping and PARP inhibitor resistance.Molecular cancer · 2024Article
- E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease.The Biochemical journal · 2024Review
- Functional Characterization of the Human BRCA1 ∆11 Splicing Isoforms in Yeast.International journal of molecular sciences · 2024Article
- Clinical significance of genetic profiling based on different anatomic sites in patients with mucosal melanoma who received or did not receive immune checkpoint inhibitors.Cancer cell international · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
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 resistance. How cancer cells achieve increased BRCA1-∆11q expression has remained unclear. Using isogenic cells with different BRCA1 mutations, we show that reduction in HUWE1 leads to increased levels of BRCA1-∆11q and PARPi resistance. This effect is specific to cells able to express BRCA1-∆11q (e.g. BRCA1 exon 11 mutant cells) and is not seen in BRCA1 mutants that cannot express BRCA1-∆11q, nor in BRCA2 mutant cells. As well as increasing levels of BRCA1-∆11q protein in exon 11 mutant cells, HUWE1 silencing also restores RAD51 nuclear foci and platinum salt resistance. HUWE1 catalytic domain mutations were also seen in a case of PARPi resistant, BRCA1 exon 11 mutant, high grade serous ovarian cancer. These results suggest how elevated levels of BRCA1-∆11q and PARPi resistance can be achieved, identify HUWE1 as a candidate biomarker of PARPi resistance for assessment in future clinical trials and illustrate how some PARPi resistance mechanisms may only operate in patients with particular BRCA1 mutations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.