ArticleMolecular cancer therapeutics2013
Chk1/2 inhibition overcomes the cisplatin resistance of head and neck cancer cells secondary to the loss of functional p53.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 125 citations in OpenAlex.
- A Phase 1b/2 Study of TP-0903 and Decitabine Targeting Mutant TP53 and/or Complex Karyotype in Patients with Untreated Acute Myeloid Leukemia ≥Age 60 Years.Cancer research communications · 2025Trial
- Preclinical analyses and phase I evaluation of LY2603618 administered in combination with pemetrexed and cisplatin in patients with advanced cancer.Investigational new drugs · 2014Trial
- Immune cell-related gene signatures for diagnostic and prognostic stratification in thyroid cancer using machine learning analysis.Discover oncology · 2026Article
- Establishment and characterization of a new immortalized human oral keratinocyte (HOK) cell line harboring various TP53 mutations.Oral oncology · 2026Article
- Combined CHK1 and PD-L1 blockade as a novel therapeutic strategy against stemness and immunosuppression in ovarian cancer.Cancer immunology, immunotherapy : CII · 2025Article
- ATR expression as a prognostic biomarker inJournal of thoracic disease · 2025Article
- RBM17 Promotes the Chemoresistance of Oral Squamous Cancer Cells Through Checkpoint Kinase 1.International journal of molecular sciences · 2025Article
- Review
- Cisplatin resistance in head and neck squamous cell carcinoma is linked to DNA damage response and cell cycle arrest transcriptomics rather than poor drug uptake.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Strategies to Overcome Intrinsic and Acquired Resistance to Chemoradiotherapy in Head and Neck Cancer.Cells · 2024Review
- The treatment landscape of triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2024Review
- Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.Experimental hematology & oncology · 2024Review
- Elimination of radiation-induced senescent cancer cells and stromal cells in vitro by near-infrared photoimmunotherapy.Cancer medicine · 2024Article
- Preclinical Evaluation of the ATR Inhibitor BAY 1895344 as a Radiosensitizer for Head and Neck Squamous Cell Carcinoma.International journal of radiation oncology, biology, physics · 2024Article
- Sponge-derived alkaloid AP-7 as a sensitizer to cisplatin in the treatment of multidrug-resistant NSCLC via Chk1-dependent mechanisms.Frontiers in pharmacology · 2024Article
- Targeting the DNA Damage Response for Cancer Therapy.International journal of molecular sciences · 2023Review
- Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review).Oncology reports · 2023Review
- Review
- Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma.Journal of the National Cancer Institute · 2022Article
- How I TreatCancers · 2022Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Despite the use of multimodality therapy using cisplatin to treat patients with advanced stage squamous cell carcinoma of the head and neck (HNSCC), there is an unacceptably high rate of treatment failure. TP53 is the most commonly mutated gene in HNSCC, and the impact of p53 mutation on response to cisplatin treatment is poorly understood. Here, we show unambiguously that wild-type TP53 (wtp53) is associated with sensitivity of HNSCC cells to cisplatin treatment, whereas mutation or loss of TP53 is associated with cisplatin resistance. We also show that senescence is the major cellular response to cisplatin in wtp53 HNSCC cells and that cisplatin resistance in p53-null or -mutant TP53 cells is due to their lack of senescence. Given the dependence on checkpoint kinase (Chk)1/2 kinases to mediate the DNA damage response in p53-deficient cells, there is potential to exploit this to therapeutic advantage through targeted inhibition of the Chk1/2 kinases. Treatment of p53-deficient HNSCC cells with the Chk inhibitor AZD7762 sensitizes them to cisplatin through induction of mitotic cell death. This is the first report showing the ability of a Chk kinase inhibitor to sensitize TP53-deficient HNSCC to cisplatin in a synthetic lethal manner, which has significance given the frequency of TP53 mutations in this disease and because cisplatin has become part of standard therapy for aggressive HNSCC tumors. These preclinical data provide evidence that a personalized approach to the treatment of HNSCC based on Chk inhibition in p53-mutant tumors may be feasible.
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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.