ArticleScientific reports2015
WEE1 kinase polymorphism as a predictive biomarker for efficacy of platinum-gemcitabine doublet chemotherapy in advanced non-small cell lung cancer patients.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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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
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- An update of predictive biomarkers related to WEE1 inhibition in cancer therapy.Journal of cancer research and clinical oncology · 2024Pooled it
- Clinical-pharmacogenetic models for personalized cancer treatment: application to malignant mesothelioma.Scientific reports · 2017Trial
- Caspase 8 polymorphisms contribute to the prognosis of advanced lung adenocarcinoma patients after platinum-based chemotherapy.Cancer biology & therapy · 2017Article
- Article
- P73 G4C14-to-A4T14 polymorphism is associated with survival in advanced non-small cell lung cancer patients.Thoracic cancer · 2017Article
- Polymorphisms ofJournal of Cancer · 2017Article
- Association ofJournal of thoracic disease · 2016Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA-damaging agents are commonly used for first-line chemotherapy of advanced non-small cell lung cancer (NSCLC). As a G2/M checkpoint kinase, Wee1 can phosphorylate CDC2-tyr15 and induce G2/M cell cycle arrest in response to DNA damage. The correlation of WEE1 polymorphisms to the efficacy of chemotherapy was tested in 663 advanced NSCLC patients. WEE1 rs3910384 genotype correlated to overall survival (OS) and progress-free survival (PFS) of NSCLC patients treated with platinum-based chemotherapy. Sub-group analysis revealed that rs3910384 was particularly associated with the efficacy of doublet chemotherapy combining two DNA-damaging agents, i.e. platinum and gemcitabine. NSCLC patients with the WEE1 rs3910384 G/G homozygote genotype showed 13.5 months extended OS, 3.2 months extended PFS, and a 274% relative increase in their 3-year survival rate (from 7.4% to 27.7%) compared to the A/A+A/G genotype after treatment with platinum-gemcitabine regimen. This finding was reproduced in the validation cohort. We utilized a luciferase reporter assay and Electrophoretic Mobility Shift Assay (EMSA) to demonstrate that rs3910384-linked WEE1 promoter haplotype can mediate allele-specific transcriptional binding and WEE1 expression in DNA damage response. In conclusion, the WEE1 rs3910384 G/G homozygote genotype can be used as a selective biomarker for NSCLC patients to indicate treatment with platinum and gemcitabine regimen.
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