ArticleCell reports2023
Multi-omics analysis reveals distinct non-reversion mechanisms of PARPi resistance in BRCA1- versus BRCA2-deficient mammary tumors.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Insights from three decades of BRCA1/2 modeling in mice.Nature genetics · 2026Review
- Review
- Review
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- SIRT5-modified human umbilical cord mesenchymal stem cells loaded with antioxidant polydopamine nanozyme enhance parpi resistance in ovarian cancer via fatty acid metabolism reprogramming.Journal of nanobiotechnology · 2025Article
- SETD1A-dependent EME1 transcription drives PARPi sensitivity in HR deficient tumour cells.British journal of cancer · 2025Article
- Synthetic lethality in cancer: a protocol for scoping review of gene interactions from synthetic lethal screens and functional studies.Systematic reviews · 2025Article
- Targeting FEN1/EXO1 to enhance efficacy of PARP inhibition in triple-negative breast cancer.Translational oncology · 2025Article
- Mechanistic insights into Rho/MRTF inhibition-induced apoptotic events and prevention of drug resistance in melanoma: implications for the involvement of pirin.Frontiers in pharmacology · 2025Article
- Preclinical studies of a PARP-targeted theranostic radiopharmaceutical for pancreatic cancer.Frontiers in pharmacology · 2025Article
- Positioning loss of PARP1 activity as the central toxic event in BRCA-deficient cancer.DNA repair · 2024Review
- Microhomology-Mediated End-Joining Chronicles: Tracing the Evolutionary Footprints of Genome Protection.Annual review of cell and developmental biology · 2024Review
- Leveraging PARP-1/2 to Target Distant Metastasis.International journal of molecular sciences · 2024Review
- 53BP1 loss elicits cGAS-STING-dependent antitumor immunity in ovarian and pancreatic cancer.Nature communications · 2024Article
- FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.EMBO molecular medicine · 2024Article
- BRCAness, DNA gaps, and gain and loss of PARP inhibitor-induced synthetic lethality.The Journal of clinical investigation · 2024Review
- C5aR1 inhibition reprograms tumor associated macrophages and reverses PARP inhibitor resistance in breast cancer.Nature communications · 2024Article
- H2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours.Nature communications · 2024Article
- PARG-deficient tumor cells have an increased dependence on EXO1/FEN1-mediated DNA repair.The EMBO journal · 2024Article
- Molecular mechanism of PARP inhibitor resistance.Oncoscience · 2024Review
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BRCA1 and BRCA2 both function in DNA double-strand break repair by homologous recombination (HR). Due to their HR defect, BRCA1/2-deficient cancers are sensitive to poly(ADP-ribose) polymerase inhibitors (PARPis), but they eventually acquire resistance. Preclinical studies yielded several PARPi resistance mechanisms that do not involve BRCA1/2 reactivation, but their relevance in the clinic remains elusive. To investigate which BRCA1/2-independent mechanisms drive spontaneous resistance in vivo, we combine molecular profiling with functional analysis of HR of matched PARPi-naive and PARPi-resistant mouse mammary tumors harboring large intragenic deletions that prevent reactivation of BRCA1/2. We observe restoration of HR in 62% of PARPi-resistant BRCA1-deficient tumors but none in the PARPi-resistant BRCA2-deficient tumors. Moreover, we find that 53BP1 loss is the prevalent resistance mechanism in HR-proficient BRCA1-deficient tumors, whereas resistance in BRCA2-deficient tumors is mainly induced by PARG loss. Furthermore, combined multi-omics analysis identifies additional genes and pathways potentially involved in modulating PARPi response.
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