ArticleJournal of the National Cancer Institute2014
mTOR co-targeting in cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations.
Article in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 107 citations in OpenAlex.
- Erlotinib and the Risk of Oral Cancer: The Erlotinib Prevention of Oral Cancer (EPOC) Randomized Clinical Trial.JAMA oncology · 2016Trial
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- The regulatory role and mechanism of energy metabolism and immune response in head and neck cancer.Genes & diseases · 2025Review
- Network Pharmacology and Molecular Docking Elucidate the Mechanism of Phillyrin in Colorectal Cancer.Food science & nutrition · 2025Article
- A Kinome-Wide Synthetic Lethal CRISPR/Cas9 Screen Reveals That mTOR Inhibition Prevents Adaptive Resistance to CDK4/CDK6 Blockade in HNSCC.Cancer research communications · 2024Article
- Interplay of p62-mTORC1 and EGFR signaling promotes cisplatin resistance in oral cancer.Heliyon · 2024Article
- Immune escape of head and neck cancer mediated by the impaired MHC-I antigen presentation pathway.Oncogene · 2024Review
- New insights into RAS in head and neck cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Article
- NSAIDs OvercomeCancers · 2022Article
- p63 Directs Subtype-Specific Gene Expression in HPV+ Head and Neck Squamous Cell Carcinoma.Frontiers in oncology · 2022Article
- EGFR Regulates the Hippo pathway by promoting the tyrosine phosphorylation of MOB1.Communications biology · 2021Article
- Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer.Nature communications · 2021Article
- Article
- Targeted Therapy as a Potential De-Escalation Strategy in Locally Advanced HPV-Associated Oropharyngeal Cancer: A Literature Review.Frontiers in oncology · 2021Review
- Precision Medicine Approaches to Overcome Resistance to Therapy in Head and Neck Cancers.Frontiers in oncology · 2021Review
- Selective inhibition of PI3K110α as a novel therapeutic strategy for cetuximab‑resistant oral squamous cell carcinoma.Oncology reports · 2020Article
- Tipifarnib as a Precision Therapy forMolecular cancer therapeutics · 2020Article
- Pathway-Specific Genome Editing of PI3K/mTOR Tumor Suppressor Genes Reveals thatMolecular cancer therapeutics · 2020Article
- Disruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer.Journal of the National Cancer Institute · 2020Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCetuximab, a monoclonal blocking antibody against the epidermal growth factor receptor EGFR, has been approved for the treatment of squamous cell carcinomas of the head and neck (HNSCC). However, only few patients display long-term responses, prompting the search for cetuximab resistance mechanisms and new therapeutic options enhancing cetuximab effectiveness.
methodsCetuximab-sensitive HNSCC cells were retro-engineered to express PIK3CA and RAS oncogenes. These cells and HNSCC cells harboring endogenous PIK3CA and RAS oncogenes were xenografted into mice (n = 10 per group) and studied for their biochemical, antitumor, antiangiogenic, and antilymphangiogenic responses to cetuximab and mTOR targeting agents. All P values are two-sided.
resultsCetuximab treatment of PIK3CA- and RAS-expressing HNSCC xenografts promoted an initial antitumor response, but all tumors relapsed within few weeks. In these tumors, cetuximab did not decrease the activity of mTOR, a downstream signaling target of EGFR, PIK3CA, and RAS. The combined administration of cetuximab and mTOR inhibitors exerted a remarkably increased antitumor activity, particularly in HNSCC cells that are resistant to cetuximab as a single agent. Indeed, cotargeting mTOR together with cetuximab caused a rapid tumor collapse of both PIK3CA- and RAS-expressing HNSCC xenografts (P < .001), concomitant with reduced proliferation (P < .001) and lymphangiogenesis (P < .001).
conclusionThe presence of PIK3CA and RAS mutations and other alterations affecting the mTOR pathway activity in HNSCC could be exploited to predict the potential resistance to cetuximab, and to select the patients that may benefit the most from the concomitant administration of cetuximab and PI3K and/or mTOR inhibitors as a precision molecular therapeutic option for HNSCC patients.
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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.