ArticleProceedings of the National Academy of Sciences of the United States of America2010
Suppression of Rev3, the catalytic subunit of Pol{zeta}, sensitizes drug-resistant lung tumors to chemotherapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 189 citations in OpenAlex.
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- Docking-Based Virtual Screening Identifies a Small-Molecule Inhibitor of the Translesion Synthesis REV7/REV3 Protein-Protein Interaction.ChemMedChem · 2026Article
- TASP1-mediated cleavage of REV3L enhances the activity of DNA polymerase ζ in mammalian cells.Nature communications · 2026Article
- Sensitization of cancer cells to DNA-damaging agents by expression of the REV1 C-terminal domain: Implications for chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Human TLS DNA polymerase: saviors or threats under replication stress?Molecular and cellular biochemistry · 2025Review
- MAD2L2 Dimerization Is Not Essential for Mitotic Regulation.International journal of molecular sciences · 2024Article
- Cryo-EM structure of the Rev1-Polζ holocomplex reveals the mechanism of their cooperativity in translesion DNA synthesis.Nature structural & molecular biology · 2024Article
- Chemoresistance Mechanisms in Non-Small Cell Lung Cancer-Opportunities for Drug Repurposing.Applied biochemistry and biotechnology · 2024Review
- Enzymatic Processing of DNA-Protein Crosslinks.Genes · 2024Review
- On Target: An Intrapulmonary Transplantation Method for Modelling Lung Tumor Development in its Native Microenvironment.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Implications of Translesion DNA Synthesis Polymerases on Genomic Stability and Human Health.Molecular and cellular biology · 2023Article
- Leveraging the replication stress response to optimize cancer therapy.Nature reviews. Cancer · 2023Review
- Article
- Division of labor within the DNA damage tolerance system reveals non-epistatic and clinically actionable targets for precision cancer medicine.Nucleic acids research · 2022Article
- Can Cisplatin Therapy Be Improved? Pathways That Can Be Targeted.International journal of molecular sciences · 2022Review
- Translesion DNA synthesis mediates acquired resistance to olaparib plus temozolomide in small cell lung cancer.Science advances · 2022Article
- New challenges in the use of nanomedicine in cancer therapy.Bioengineered · 2022Article
- Identifying Novel Psoriatic Disease Drug Targets Using a Genetics-Based Priority Index Pipeline.Journal of psoriasis and psoriatic arthritis · 2021Article
- Implications of inhibition of Rev1 interaction with Y family DNA polymerases for cisplatin chemotherapy.Genes & development · 2021Article
- Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy.International journal of molecular sciences · 2021Review
55 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Platinum-based chemotherapeutic drugs are front-line therapies for the treatment of non-small cell lung cancer. However, intrinsic drug resistance limits the clinical efficacy of these agents. Recent evidence suggests that loss of the translesion polymerase, Polζ, can sensitize tumor cell lines to cisplatin, although the relevance of these findings to the treatment of chemoresistant tumors in vivo has remained unclear. Here, we describe a tumor transplantation approach that enables the rapid introduction of defined genetic lesions into a preclinical model of lung adenocarcinoma. Using this approach, we examined the effect of impaired translesion DNA synthesis on cisplatin response in aggressive late-stage lung cancers. In the presence of reduced levels of Rev3, an essential component of Polζ, tumors exhibited pronounced sensitivity to cisplatin, leading to a significant extension in overall survival of treated recipient mice. Additionally, treated Rev3-deficient cells exhibited reduced cisplatin-induced mutation, a process that has been implicated in the induction of secondary malignancies following chemotherapy. Taken together, our data illustrate the potential of Rev3 inhibition as an adjuvant therapy for the treatment of chemoresistant malignancies, and highlight the utility of rapid transplantation methodologies for evaluating mechanisms of chemotherapeutic resistance in preclinical 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.