ArticleGenes, chromosomes & cancer2014
Targeted inhibition of ATR or CHEK1 reverses radioresistance in oral squamous cell carcinoma cells with distal chromosome arm 11q loss.
Article in Genes, chromosomes & cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
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- B lymphocytes and tertiary lymphoid structures have a prognostic impact on penile squamous cell carcinoma.The journal of pathology. Clinical research · 2025Article
- FTO enhances OSCC progression via m⁶A-dependent stabilization of PKM2 mRNA through YTHDF2 modulation.Head & face medicine · 2025Article
- Editorial: Overcoming therapeutic resistance in head and neck squamous cell carcinoma.Frontiers in oncology · 2025Article
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- Tissue microarray analyses of the essential DNA repair factors ATM, DNA-PKcs and Ku80 in head and neck squamous cell carcinoma.Radiation oncology (London, England) · 2024Article
- Inhibition of key DNA double strand break repair protein kinases enhances radiosensitivity of head and neck cancer cells to X-ray and proton irradiation.Cell death discovery · 2024Article
- Overcoming Resistance to Standard-of-Care Therapies for Head and Neck Squamous Cell Carcinomas.Cells · 2024Review
- 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
- MiRNA-related metastasis in oral cancer: moving and shaking.Cancer cell international · 2023Review
- Recent Advances in Synergistic Antitumor Effects Exploited from the Inhibition of Ataxia Telangiectasia and RAD3-Related Protein Kinase (ATR).Molecules (Basel, Switzerland) · 2022Review
- Pharmacologic inhibition of ataxia telangiectasia and Rad3-related (ATR) in the treatment of head and neck squamous cell carcinoma.Molecular carcinogenesis · 2022Review
- A Promising, Novel Radiosensitizer Nanodrug Complex for Oral Cavity Cancer: Cetuximab and Cisplatin-Conjugated Gold Nanoparticles.Balkan medical journal · 2021Article
- Review
- IRAK2, an IL1R/TLR Immune Mediator, Enhances RadiosensitivityFrontiers in oncology · 2021Article
- R2TP/PAQosome as a promising chemotherapeutic target in cancer.The Japanese dental science review · 2020Review
- Transcriptomic analysis on the effects of melatonin in gastrointestinal carcinomas.BMC gastroenterology · 2020Article
- The radiobiology of HPV-positive and HPV-negative head and neck squamous cell carcinoma.Expert reviews in molecular medicine · 2020Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Oral squamous cell carcinoma (OSCC), a subset of head and neck squamous cell carcinoma (HNSCC), is the eighth most common cancer in the U.S.. Amplification of chromosomal band 11q13 and its association with poor prognosis has been well established in OSCC. The first step in the breakage-fusion-bridge (BFB) cycle leading to 11q13 amplification involves breakage and loss of distal 11q. Distal 11q loss marked by copy number loss of the ATM gene is observed in 25% of all Cancer Genome Atlas (TCGA) tumors, including 48% of HNSCC. We showed previously that copy number loss of distal 11q is associated with decreased sensitivity (increased resistance) to ionizing radiation (IR) in OSCC cell lines. We hypothesized that this radioresistance phenotype associated with ATM copy number loss results from upregulation of the compensatory ATR-CHEK1 pathway, and that knocking down the ATR-CHEK1 pathway increases the sensitivity to IR of OSCC cells with distal 11q loss. Clonogenic survival assays confirmed the association between reduced sensitivity to IR in OSCC cell lines and distal 11q loss. Gene and protein expression studies revealed upregulation of the ATR-CHEK1 pathway and flow cytometry showed G2 M checkpoint arrest after IR treatment of cell lines with distal 11q loss. Targeted knockdown of the ATR-CHEK1 pathway using CHEK1 or ATR siRNA or a CHEK1 small molecule inhibitor (SMI, PF-00477736) resulted in increased sensitivity of the tumor cells to IR. Our results suggest that distal 11q loss is a useful biomarker in OSCC for radioresistance that can be reversed by ATR-CHEK1 pathway inhibition.
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