ArticleOncotarget2016
Co-inhibition of pol θ and HR genes efficiently synergize with cisplatin to suppress cisplatin-resistant lung cancer cells survival.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- Combining Artificial Intelligence and Human Expertise in Pursuit of Novel PolQ Inhibitors.ACS omega · 2026Article
- Emerging insights into alternative end‑joining: Mechanisms, genome instability and therapeutic opportunities in cancer (Review).International journal of oncology · 2025Review
- RTx-303, an Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates PARP Inhibitors in BRCA Mutant Tumors.Journal of medicinal chemistry · 2025Article
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- Polθ: emerging synthetic lethal partner in homologous recombination-deficient tumors.Cancer gene therapy · 2024Review
- Structural basis for a Polθ helicase small-molecule inhibitor revealed by cryo-EM.Nature communications · 2024Article
- Discovery of a small-molecule inhibitor that traps Polθ on DNA and synergizes with PARP inhibitors.Nature communications · 2024Article
- Role of Translesion DNA Synthesis in the Metabolism of Replication-associated Nascent Strand Gaps.Journal of molecular biology · 2024Review
- Fanconi anemia-associated chromosomal radial formation is dependent on POLθ-mediated alternative end joining.Cell reports · 2023Article
- Small Molecules Targeting DNA Polymerase Theta (POLθ) as Promising Synthetic Lethal Agents for Precision Cancer Therapy.Journal of medicinal chemistry · 2023Review
- Review
- Multifaceted Nature of DNA Polymerase θ.International journal of molecular sciences · 2023Review
- Polθ Inhibition: An Anticancer Therapy for HR-Deficient Tumours.International journal of molecular sciences · 2022Review
- Identification ofJournal of medicinal chemistry · 2022Article
- Synthetic Lethality Targeting Polθ.Genes · 2022Review
- Targeting the replication stress response through synthetic lethal strategies in cancer medicine.Trends in cancer · 2021Review
- Review
- Genome-wide CRISPR screens reveal cyclin C as synthetic survival target of BRCA2.Nucleic acids research · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cisplatin exert its anticancer effect by creating intrastrand and interstrand DNA cross-links which block DNA replication and is a major drug used to treat lung cancer. However, the main obstacle of the efficacy of treatment is drug resistance. Here, we show that expression of translesion synthesis (TLS) polymerase Q (POLQ) was significantly elevated by exposure of lung cancer cells A549/DR (a cisplatin-resistant A549 cell line) to cisplatin. POLQ expression correlated inversely with homologous recombination (HR) activity. Co-depletion of BRCA2 and POLQ by siRNA markedly increased sensitivity of A549/DR cells to cisplatin, which was accompanied with impairment of double strand breaks (DSBs) repair reflected by prominent cell cycle checkpoint response, increased chromosomal aberrations and persistent colocalization of p-ATM and 53BP1 foci induced by cisplatin. Thus, co-knockdown of POLQ and HR can efficiently synergize with cisplatin to inhibit A549/DR cell survival by inhibiting DNA DSBs repair. Similar results were observed in A549/DR cells co-depleted of BRCA2 and POLQ following BMN673 (a PARP inhibitor) treatment. Importantly, the sensitization effects to cisplatin and BMN673 in A549/DR cells by co-depleting BRCA2 and POLQ was stronger than those by co-depleting BRCA2 and other TLS factors including POLH, REV3, or REV1. Our results indicate that there is a synthetic lethal relationship between pol θ-mediated DNA repair and HR pathways. Pol θ may be considered as a novel target for lung cancer therapy.
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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.