ArticleLung cancer (Amsterdam, Netherlands)2013
CHK1 levels correlate with sensitization to pemetrexed by CHK1 inhibitors in non-small cell lung cancer cells.
Article in Lung cancer (Amsterdam, Netherlands), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
- A CHK1-mediated phosphorylation switch suppresses human Topoisomerase 1-associated genomic instability.The EMBO journal · 2026Article
- Comparative effects of arsenic trioxide and chemotherapy on Chk1 and CDC25 gene expression in gastric cancer cells AGS and MKN45: a potential therapeutic strategy.Molecular biology reports · 2025Article
- Exploring the mechanism of 6-Methoxydihydrosanguinarine in the treatment of lung adenocarcinoma based on network pharmacology, molecular docking and experimental investigation.BMC complementary medicine and therapies · 2024Article
- Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review.Translational lung cancer research · 2024Review
- Exploration of the carcinogenetic and immune role of CHK1 in human cancer.Journal of Cancer · 2024Article
- Targeting the DNA Damage Response for Cancer Therapy.International journal of molecular sciences · 2023Review
- A landscape of response to drug combinations in non-small cell lung cancer.Nature communications · 2023Article
- A review of recent advances in the novel therapeutic targets and immunotherapy for lung cancer.Medical oncology (Northwood, London, England) · 2023Review
- Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma.Oncology · 2023Article
- Identification of Potential Key Genes and Prognostic Biomarkers of Lung Cancer Based on Bioinformatics.BioMed research international · 2023Article
- Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer Patients.Biomedicines · 2022Article
- Chk1 Inhibition Ameliorates Alzheimer's Disease Pathogenesis and Cognitive Dysfunction Through CIP2A/PP2A Signaling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Mechanisms of resistance to chemotherapy in non-small cell lung cancer.Archives of pharmacal research · 2021Review
- Targeting Non-Oncogene Addiction for Cancer Therapy.Biomolecules · 2021Review
- Article
- Mechanisms of resistance to pemetrexed in non-small cell lung cancer.Translational lung cancer research · 2019Review
- Checkpoint Kinase 1 Inhibition Enhances Cisplatin Cytotoxicity and Overcomes Cisplatin Resistance in SCLC by Promoting Mitotic Cell Death.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2019Article
- ATR/CHK1 inhibitors and cancer therapy.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2018Review
- The cell cycle checkpoint inhibitors in the treatment of leukemias.Journal of hematology & oncology · 2017Review
- Chk1 inhibition potentiates the therapeutic efficacy of PARP inhibitor BMN673 in gastric cancer.American journal of cancer research · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveOverexpression of checkpoint kinase 1 (CHK1) is associated with poorer patient outcome and therapeutic resistance in multiple tumor models. Inhibition of CHK1 has been proposed as a strategy to increase the effectiveness of chemotherapeutic agents, especially in p53-deficient tumors. In this study, we evaluated the effects of a novel CHK1 inhibitor, MK-8776, in combination with pemetrexed (PMX) on cell proliferation and survival in a panel of p53 mutant non-small cell lung cancer (NSCLC) cell lines.
methodsWe examined CHK1 expression in 442 resected lung adenocarcinoma specimens using Affymetrix U133A gene expression arrays. We correlated CHK1 mRNA expression with patient survival, tumor differentiation and genomic complexity. We evaluated CHK1 levels in NSCLC cell lines and identified four p53 mutant cell lines with variable CHK1 expression (H1993, H23, H1437 and H1299) based on publicly available gene expression data. We confirmed differential CHK1 mRNA and CHK1 protein levels by qRT-PCR, ELISA, Western Blot analysis (WB) and immunohistochemistry. We examined cell line sensitization to PMX in response to CHK1 inhibition with MK-8776 using WST-1 and clonogenic survival assays.
resultsWe found that elevated CHK1 expression in primary lung adenocarcinomas correlates with poor tumor differentiation and significantly worse patient survival. Tumors with elevated CHK1 mRNA levels have a higher number of gene mutations and DNA copy number gain or amplifications. CHK1 inhibition by MK-8776 enhances sensitivity of NSCLC cell lines to PMX. CHK1 mRNA and protein expression are variable among NSCLC cell lines, and cells expressing higher levels of CHK1 protein are more sensitive to the CHK1 inhibition by MK-8776 as compared to low CHK1 expressing cells.
conclusionsThese findings suggest that CHK1 levels may not only serve as a biomarker of poor prognosis in surgically-resected lung adenocarcinomas, but could also be a predictive marker for CHK1 inhibitor sensitivity, pending in vivo and clinical confirmation.
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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.