ArticleInternational journal of cancer2019
PARP inhibitors synergize with gemcitabine by potentiating DNA damage in non-small-cell lung cancer.
Article in International journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- DNA damage response signature-based prognostic genes for intrahepatic cholangiocarcinoma: a combined analysis of machine learning and biological experiments.Cancer cell international · 2026Article
- Enhancing the Nucleoside Analog Response with Translational Therapeutic Approaches to Overcome Resistance.Cells · 2026Review
- Olaparib synergy screen reveals Exemestane induces replication stress in triple-negative breast cancer.Molecular oncology · 2025Article
- The Prognostic Value of the XPC rs2228001 Single Nucleotide Polymorphism in Cholangiocarcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Alterations and correlation between DNA damage and repair response and PD-L1 expression in non-small cell lung cancers.BMC cancer · 2025Article
- CldU sensitizesFrontiers in oncology · 2025Article
- PARP inhibition increases sensitivity to cisplatin in non-small-cell lung carcinoma via the induction of TET-dependent hydroxymethylation.Frontiers in cell and developmental biology · 2025Article
- Review
- A novel targeted NGS panel identifies numerous homologous recombination deficiency (HRD)-associated gene mutations in addition to known BRCA mutations.Diagnostic pathology · 2024Article
- Evofosfamide and Gemcitabine Act Synergistically in Pancreatic Cancer Xenografts by Dual Action on Tumor Vasculature and Inhibition of Homologous Recombination DNA Repair.Antioxidants & redox signaling · 2023Article
- Altered cytoplasmic and nuclear ADP-ribosylation levels analyzed with an improved ADP-ribose binder are a prognostic factor in renal cell carcinoma.The journal of pathology. Clinical research · 2023Article
- Discovery of Ruthenium(II) Metallocompound and Olaparib Synergy for Cancer Combination Therapy.Journal of medicinal chemistry · 2023Article
- STL127705 synergize with olaparib in castration-resistant prostate cancer by inhibiting homologous recombination and non-homologous end-joining repair.American journal of cancer research · 2023Article
- Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas.International journal of molecular sciences · 2022Article
- Review
- Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer.Nature reviews. Cancer · 2022Review
- Precision Medicine forCancers · 2022Review
- Genetic Variants in Double-Strand Break Repair Pathway Genes to Predict Platinum-Based Chemotherapy Prognosis in Patients With Lung Cancer.Frontiers in pharmacology · 2022Article
- Current status and future perspectives of immune checkpoint inhibitors in extensive-stage small cell lung cancer.American journal of cancer research · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated great promise in the treatment of patients with deficiencies in homologous recombination (HR) DNA repair, such as those with loss of BRCA1 or BRCA2 function. However, emerging studies suggest that PARP inhibition can also target HR-competent cancers, such as non-small-cell lung cancer (NSCLC), and that the therapeutic effect of PARP inhibition may be improved by combination with chemotherapy agents. In our study, it was found that PARP inhibitors talazoparib (BMN-673) and olaparib (AZD-2281) both had synergistic activity with the common first-line chemotherapeutic gemcitabine in a panel of lung cancer cell lines. Furthermore, the combination demonstrated significant in vivo antitumor activity in an H23 xenograft model of NSCLC compared to either agent as monotherapy. This synergism occurred without loss of HR repair efficiency. Instead, the combination induced synergistic single-strand DNA breaks, leading to accumulation of toxic double-strand DNA lesions in vitro and in vivo. Our study elucidates the underlying mechanisms of synergistic activity of PARP inhibitors and gemcitabine, providing a strong motivation to pursue this combination as an improved therapeutic regimen.
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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.