ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2019
Checkpoint Kinase 1 Inhibition Enhances Cisplatin Cytotoxicity and Overcomes Cisplatin Resistance in SCLC by Promoting Mitotic Cell Death.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers.
What it found
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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.
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Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.Annals of medicine · 2026Review
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- Increased vulnerability of colorectal cancer models with high alkylation damage to NTHL1 inactivation.Scientific reports · 2026Article
- Pharmacological WEE1 inhibition as a strategy to overcome cisplatin resistance in non-seminoma testicular cancer: insights from preclinical models.Scientific reports · 2026Article
- INCENP and CDCA8 predict neoadjuvant chemotherapy response and outcomes in esophageal squamous cell carcinoma.Nature communications · 2026Article
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- Effectiveness of Atezolizumab in Addition to Chemotherapy in ES-SCLC: A Retrospective Real-World Monocentric Study.Cancers · 2025Article
- Molecular Features and Actionable Gene Targets of Testicular Germ Cell Tumors in a Real-World Setting.International journal of molecular sciences · 2025Article
- Differential Molecular Transcriptomics and Underlying Biological Pathways between Smokers Lung Cancer (Small Cell Lung Carcinoma) in Comparison to Healthy Human Lung Cells.Computational molecular bioscience · 2025Article
- Review
- Antitumor Activity of Radiation Therapy Combined with Checkpoint Kinase Inhibition in SHH/International journal of molecular sciences · 2025Article
- CHK1 inhibition overcomes gemcitabine resistance in non-small cell lung cancer cell A549.Molecular & cellular oncology · 2025Article
- Article
- Review
- Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.Experimental hematology & oncology · 2024Review
- RHBDF1 modulates cisplatin sensitivity of small cell lung cancer through YAP1/Smad2 signaling pathway.Heliyon · 2024Article
- Molecular and Pathologic Characterization of YAP1-Expressing Small Cell Lung Cancer Cell Lines Leads to Reclassification as SMARCA4-Deficient Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Article
- Actionable Driver Events in Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
- Risk factors of early mortality in patients with small cell lung cancer: a retrospective study in the SEER database.Journal of cancer research and clinical oncology · 2023Article
Corrections and comments
- Erratum issuedErratum.2019
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionPlatinum-based chemotherapy remains the standard treatment for patients with SCLC, but the benefit of the treatment is often hampered by rapid development of drug resistance. Thus far, there is no targeted therapy available for SCLC. More than 90% of SCLC tumors harbor mutations in the tumor suppressor gene tumor protein p53 (p53), an important DNA damage checkpoint regulator, and these tumor cells rely predominantly on the checkpoint kinases to control DNA damage response.
methodsWe examined whether and how inhibition of checkpoint kinase 1 (Chk1) affects cisplatin cytotoxicity in SCLC cells with and without p53 mutations, and evaluated the effect of Chk1 inhibitor and cisplatin combination in cisplatin-sensitive and -resistant preclinical models.
resultsInhibition of Chk1 synergized with cisplatin to induce mitotic cell death in the p53-deficeint SCLC cells. The effect was regulated in part through activation of caspase 2 and downregulation of E2F transcription factor 1 (E2F1). Furthermore, Chk1 inhibitors prexasertib and AZD7762 enhanced cisplatin antitumor activity and overcame cisplatin resistance in SCLC preclinical models in vitro an in vivo. We also observed that higher expression of Chk1 was associated with poorer overall survival of patients with SCLC.
conclusionsOur data account Chk1 as a potential therapeutic target in SCLC, and rationalize clinical development of Chk1 inhibitor and cisplatin combinational strategy for the treatment of SCLC.
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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.