ArticleScience advances2022
Translesion DNA synthesis mediates acquired resistance to olaparib plus temozolomide in small cell lung cancer.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The trial behind it
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- The PIK3CA/AKT pathway drives therapy resistance in rhabdomyosarcoma.Nature communications · 2025Article
- Human TLS DNA polymerase: saviors or threats under replication stress?Molecular and cellular biochemistry · 2025Review
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- DNA damage response signatures are associated with frontline chemotherapy response and routes of tumor evolution in extensive stage small cell lung cancer.Molecular cancer · 2025Article
- Review
- CHD6 has poly(ADP-ribose)- and DNA-binding domains and regulates PARP1/2-trapping inhibitor sensitivity via abasic site repair.Nature communications · 2025Article
- Distinct effects of sacituzumab govitecan and berzosertib on DNA damage response in ovarian cancer.iScience · 2024Article
- Unprocessed genomic uracil as a source of DNA replication stress in cancer cells.Molecular cell · 2024Article
- Lead compound profiling for small molecule inhibitors of the REV1-CT/RIR Translesion synthesis Protein-Protein interaction.Bioorganic & medicinal chemistry · 2024Article
- Acquired Cross-Resistance in Small Cell Lung Cancer due to Extrachromosomal DNA Amplification of MYC Paralogs.Cancer discovery · 2024Article
- Enzymatic Processing of DNA-Protein Crosslinks.Genes · 2024Review
- REV7: a small but mighty regulator of genome maintenance and cancer development.Frontiers in oncology · 2024Review
- CDKN1A/p21 in Breast Cancer: Part of the Problem, or Part of the Solution?International journal of molecular sciences · 2023Review
- Response of the Urothelial Carcinoma Cell Lines to Cisplatin.International journal of molecular sciences · 2022Article
- Nucleobase-modified nucleosides and nucleotides: Applications in biochemistry, synthetic biology, and drug discovery.Frontiers in chemistry · 2022Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
In small cell lung cancer (SCLC), acquired resistance to DNA-damaging therapy is challenging to study because rebiopsy is rarely performed. We used patient-derived xenograft models, established before therapy and after progression, to dissect acquired resistance to olaparib plus temozolomide (OT), a promising experimental therapy for relapsed SCLC. These pairs of serial models reveal alterations in both cell cycle kinetics and DNA replication and demonstrate both inter- and intratumoral heterogeneity in mechanisms of resistance. In one model pair, up-regulation of translesion DNA synthesis (TLS) enabled tolerance of OT-induced damage during DNA replication. TLS inhibitors restored sensitivity to OT both in vitro and in vivo, and similar synergistic effects were seen in additional SCLC cell lines. This represents the first described mechanism of acquired resistance to DNA damage in a patient with SCLC and highlights the potential of the serial model approach to investigate and overcome resistance to therapy in SCLC.
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Registered trials
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