ArticleBritish journal of cancer2021
Targeting autophagy reverses de novo resistance in homologous recombination repair proficient breast cancers to PARP inhibition.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Mechanisms of synergistic action between olaparib and KPT-330 in pancreatic cancer.Cell biology and toxicology · 2026Article
- CRISPR screen identifies autophagy inhibition (GNS561) as a PARP inhibitor (AZD5305) combination strategy in small cell lung cancer.Cancer & metabolism · 2026Article
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- Autophagy impairs the sensitivity of Ewing sarcoma cells to PARP inhibitors.Cancer chemotherapy and pharmacology · 2026Article
- Development of Stearic Acid Nanoemulsion for Therapeutic Delivery of Talazoparib Against Breast Cancer.Pharmaceutics · 2026Article
- Removing therapy-induced senescent cancer cells targets and potentiates the response of pancreatic cancer cells toward PARP inhibitors as maintenance therapy.Apoptosis : an international journal on programmed cell death · 2026Article
- Epigenetic Regulation of Autophagy in Breast Cancer: Implications for Biomarker Discovery and Personalized Therapy.Cancer reports (Hoboken, N.J.) · 2025Review
- PARP inhibitor BMN673 triggers PARylation-mediated ATF4-GDF15 pathway to drive autophagy and ferroptosis in ataxia telangiectasia mutated gene-deficient colorectal cancer cells.Molecular biomedicine · 2025Article
- An overview of autophagy inhibition as a potential clinical strategy in cancer therapy.Molecular pharmacology · 2025Review
- Article
- Targeting Replication Fork Processing Synergizes with PARP Inhibition to Potentiate Lethality in Homologous Recombination Proficient Ovarian Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Astragalus polysaccharides sensitize ovarian cancer stem cells to PARPi by inhibiting mitophagy via PINK1/Parkin signaling.iScience · 2024Article
- Studies on the mechanism of local and extra-intestinal tissue manifestations in AOM-DSS-induced carcinogenesis in BALB/c mice: role of PARP-1, NLRP3, and autophagy.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- KPT330 promotes the sensitivity of glioblastoma to olaparib by retaining SQSTM1 in the nucleus and disrupting lysosomal function.Autophagy · 2024Article
- Nanoplatform-Mediated Autophagy Regulation and Combined Anti-Tumor Therapy for Resistant Tumors.International journal of nanomedicine · 2024Review
- Article
- Suppression of GCH1 Sensitizes Ovarian Cancer and Breast Cancer to PARP Inhibitor.Journal of oncology · 2023Article
- BMN673 Is a PARP Inhibitor with Unique Radiosensitizing Properties: Mechanisms and Potential in Radiation Therapy.Cancers · 2022Review
- Development of Olaparib-Resistance Prostate Cancer Cell Lines to Identify Mechanisms Associated with Acquired Resistance.Cancers · 2022Article
- Is autophagy induction by PARP inhibitors a target for therapeutic benefit?Oncology research · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPoly(ADP-ribose) polymerase inhibitors (PARPi) target tumours defective in homologous recombination (HR). Most BRCA-wild-type (WT) HR-proficient breast cancers are intrinsically resistant to PARP inhibitors, e.g., talazoparib. We evaluated the role of autophagy in this de novo resistance and determined the underlying mechanism to overcome this.
methodsAutophagosome formation and autophagic flux were assessed by evaluating endogenous LC3-II levels and ectopic expression of EGFP-LC3 and mRFP-EGFP-LC3 in breast cancer cells. Autophagy-defective cells were generated by genetic depletion of BECN1, ATG5, p62/SQSTM1 and LAMP1 by using CRISPR-Cas9 double nickase system. The response of PARPi was evaluated in autophagy-proficient and -defective breast cancer cells and in xenograft SCID-mice model.
resultsPro-survival autophagy was significantly enhanced upon talazoparib treatment in BRCA-WT breast cancer cell lines. Autophagy-deficient cells were hypersensitive to talazoparib. Targeting autophagy synergistically enhanced the therapeutic efficacy of talazoparib in BRCA1-WT breast cancer cells in vitro and in vivo xenograft tumour mouse model. Mechanistically, autophagy inhibition by chloroquine promoted deleterious NHEJ mediated DSB-repair, leading to extensive genomic instability and mitotic catastrophe.
conclusionsAutophagy confers de novo resistance to PARP inhibitor, talazoparib. Autophagy inhibition improves the therapeutic outcome of PARPi treatment in preclinical mice model, bearing HR-proficient breast tumours, warranting its usage in the clinical settings.
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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.