ArticleMolecular oncology2021
Acquired small cell lung cancer resistance to Chk1 inhibitors involves Wee1 up-regulation.
Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 27 citations in OpenAlex.
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- The CHK1 inhibitor Prexasertib is effective againstFrontiers in endocrinology · 2026Article
- Next Generation DNA Damage Response Inhibitors: Harnessing Nanocarriers and Tumor Microenvironment for Precision Cancer Therapy.Oncology research · 2026Review
- ATR-CHK1 Axis Inhibitors in Gastric Cancer Treatment.International journal of molecular sciences · 2025Review
- Combining serum CDK1 with tumor markers for the diagnosis of small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Current and future therapies for small cell lung carcinoma.Journal of hematology & oncology · 2025Review
- Review
- AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis.Science China. Life sciences · 2025Article
- Advances in immuno-based and targeted therapies in extensive-stage small cell lung cancer.Therapeutic advances in medical oncology · 2025Review
- Review
- The Role of ADCY1 in Regulating the Sensitivity of Platinum-Based Chemotherapy in NSCLC.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.Experimental hematology & oncology · 2024Review
- The Role of Transglutaminase 2 in Cancer: An Update.International journal of molecular sciences · 2024Review
- Promises of Protein Kinase Inhibitors in Recalcitrant Small-Cell Lung Cancer: Recent Scenario and Future Possibilities.Cancers · 2024Review
- Actionable Driver Events in Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
- Smoking induces WEE1 expression to promote docetaxel resistance in esophageal adenocarcinoma.Molecular therapy oncolytics · 2023Article
- Synthetic and Medicinal Chemistry Approaches Toward WEE1 Kinase Inhibitors and Its Degraders.ACS omega · 2023Review
- A review of recent advances in the novel therapeutic targets and immunotherapy for lung cancer.Medical oncology (Northwood, London, England) · 2023Review
- Keeping RelApse in Chk: molecular mechanisms of Chk1 inhibitor resistance in lymphoma.The Biochemical journal · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Platinum-based chemotherapy has been the cornerstone treatment for small cell lung cancer (SCLC) for decades, but no major progress has been made in the past 20 years with regard to overcoming chemoresistance. As the cell cycle checkpoint kinase 1 (Chk1) plays a key role in DNA damage response to chemotherapeutic drugs, we explored the mechanisms of acquired drug resistance to the Chk1 inhibitor prexasertib in SCLC. We established prexasertib resistance in two SCLC cell lines and found that DNA copy number, messengerRNA (mRNA) and protein levels of the cell cycle regulator Wee1 significantly correlate with the level of acquired resistance. Wee1 small interfering RNA (siRNA) or Wee1 inhibitor reversed prexasertib resistance, whereas Wee1 transfection induced prexasertib resistance in parental cells. Reverse phase protein microarray identified up-regulated proteins in the resistant cell lines that are involved in apoptosis, cell proliferation and cell cycle. Down-regulation of CDK1 and CDC25C kinases promoted acquired resistance in parental cells, whereas down-regulation of p38MAPK reversed the resistance. High Wee1 expression was significantly correlated with better prognosis of resected SCLC patients. Our results indicate that Wee1 overexpression plays an important role in acquired resistance to Chk1 inhibition. We also show that bypass activation of the p38MAPK signaling pathway may contribute to acquired resistance to Chk1 inhibition. The combination of Chk1 and Wee1 inhibitors may provide a new therapeutic 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.