ArticleBritish journal of cancer2014
The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models.
Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 86 citations in OpenAlex.
- CRISPR Screens Identify PIK3C2A as a Novel Mediator of EGFR Inhibitor Resistance in Head and Neck Squamous Cell Carcinoma.Head & neck · 2026Article
- In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma.Drug delivery · 2025Article
- A first-in-class selective inhibitor of EGFR and PI3K offers a single-molecule approach to targeting adaptive resistance.Nature cancer · 2024Article
- Overcoming Resistance to Standard-of-Care Therapies for Head and Neck Squamous Cell Carcinomas.Cells · 2024Review
- Multi-kinase compensation rescues EGFR knockout in a cell line model of head and neck squamous cell carcinoma.Archives of oral biology · 2023Article
- Platycodin D represses β-catenin to suppress metastasis of cetuximab-treated KRAS wild-type colorectal cancer cells.Clinical & experimental metastasis · 2023Article
- Establishment of head and neck squamous cell carcinoma mouse models for cetuximab resistance and sensitivity.Cancer drug resistance (Alhambra, Calif.) · 2023Article
- Article
- Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.Head & neck · 2022Article
- Comprehensive Molecular Landscape of Cetuximab Resistance in Head and Neck Cancer Cell Lines.Cells · 2022Article
- The PI3K/mTOR inhibitor Gedatolisib eliminates dormant breast cancer cells in organotypic culture, but fails to prevent metastasis in preclinical settings.Molecular oncology · 2022Article
- Platycodin D sensitizesFrontiers in oncology · 2022Article
- p63 Directs Subtype-Specific Gene Expression in HPV+ Head and Neck Squamous Cell Carcinoma.Frontiers in oncology · 2022Article
- Phase I trial of copanlisib, a selective PI3K inhibitor, in combination with cetuximab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.Investigational new drugs · 2021Article
- A phospho-proteomic study of cetuximab resistance in KRAS/NRAS/BRAFCellular oncology (Dordrecht, Netherlands) · 2021Article
- Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma.Cancers · 2021Article
- New Therapeutic Opportunities for the Treatment of Squamous Cell Carcinomas: A Focus on Novel Driver Kinases.International journal of molecular sciences · 2021Review
- Autophagy-targeted therapy to modulate age-related diseases: Success, pitfalls, and new directions.Current research in pharmacology and drug discovery · 2021Review
- miR-328-3p promotes migration and invasion by targeting H2AFX in head and neck squamous cell carcinoma.Journal of Cancer · 2021Article
- Precision Medicine Approaches to Overcome Resistance to Therapy in Head and Neck Cancers.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCetuximab is the only targeted agent approved for the treatment of head and neck squamous cell carcinomas (HNSCC), but low response rates and disease progression are frequently reported. As the phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways have an important role in the pathogenesis of HNSCC, we investigated their involvement in cetuximab resistance.
methodsDifferent human squamous cancer cell lines sensitive or resistant to cetuximab were tested for the dual PI3K/mTOR inhibitor PF-05212384 (PKI-587), alone and in combination, both in vitro and in vivo.
resultsTreatment with PKI-587 enhances sensitivity to cetuximab in vitro, even in the condition of epidermal growth factor receptor (EGFR) resistance. The combination of the two drugs inhibits cells survival, impairs the activation of signalling pathways and induces apoptosis. Interestingly, although significant inhibition of proliferation is observed in all cell lines treated with PKI-587 in combination with cetuximab, activation of apoptosis is evident in sensitive but not in resistant cell lines, in which autophagy is pre-eminent. In nude mice xenografted with resistant Kyse30 cells, the combined treatment significantly reduces tumour growth and prolongs mice survival.
conclusionsPhosphoinositide 3-kinase/mammalian target of rapamycin inhibition has an important role in the rescue of cetuximab resistance. Different mechanisms of cell death are induced by combined treatment depending on basal anti-EGFR responsiveness.
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