ArticleMolecular oncology2013
A patient tumor transplant model of squamous cell cancer identifies PI3K inhibitors as candidate therapeutics in defined molecular bins.
Article in Molecular oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 164 citations in OpenAlex.
- A Phase 1b/2 Study of Alpelisib in Combination with Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.Targeted oncology · 2023Trial
- Trial
- From HPV infection to cervical precancer: Molecular mechanisms, immune microenvironment and emerging technologies.Cellular and molecular life sciences : CMLS · 2026Review
- Autologous Thymic Organoids Support Functional T-cell Education and Enhance Antitumor Immunity in Humanized Mice with Melanoma Xenografts.Cancer research communications · 2025Article
- Improved Methods for the Stable Generation of Human Papillomavirus-Driven Head and Neck Cancer Cell Lines.Molecular carcinogenesis · 2025Article
- Extracellular vesicle-mediated gene therapy targets BRAFJournal of nanobiotechnology · 2025Article
- Renal capsule patient-derived xenograft model for gastric cancer: establishment and MRI characterization.Frontiers in immunology · 2025Article
- Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes.Nature communications · 2024Article
- Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma.Nature communications · 2024Article
- The Role of the PI3K/Akt/mTOR Axis in Head and Neck Squamous Cell Carcinoma.Biomedicines · 2024Review
- Patient-Derived-Xenografts in Mice: A Preclinical Platform for Cancer Research.Cold Spring Harbor perspectives in medicine · 2024Review
- Network pharmacology: an efficient but underutilized approach in oral, head and neck cancer therapy-a review.Frontiers in pharmacology · 2024Review
- TAM family kinases as therapeutic targets at the interface of cancer and immunity.Nature reviews. Clinical oncology · 2023Review
- HPV-positive murine oral squamous cell carcinoma: development and characterization of a new mouse tumor model for immunological studies.Journal of translational medicine · 2023Article
- PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.Biology · 2023Review
- Cancer-associated fibroblasts are the main contributors to epithelial-to-mesenchymal signatures in the tumor microenvironment.Scientific reports · 2023Article
- Therapeutic implications of transcriptomics in head and neck cancer patient-derived xenografts.PloS one · 2023Article
- Single-cell RNA sequencing revealed subclonal heterogeneity and gene signatures of gemcitabine sensitivity in pancreatic cancer.Frontiers in pharmacology · 2023Article
- Application status and future prospects of the PDX model in lung cancer.Frontiers in oncology · 2023Review
- Novel Systemic Treatment Modalities Including Immunotherapy and Molecular Targeted Therapy for Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2022Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
32 authors at 4 institutions in 1 country.
Funding
Abstract
Targeted therapy development in head and neck squamous cell carcinoma (HNSCC) is challenging given the rarity of activating mutations. Additionally, HNSCC incidence is increasing related to human papillomavirus (HPV). We sought to develop an in vivo model derived from patients reflecting the evolving HNSCC epidemiologic landscape, and use it to identify new therapies. Primary and relapsed tumors from HNSCC patients, both HPV+ and HPV-, were implanted on mice, giving rise to 25 strains. Resulting xenografts were characterized by detecting key mutations, measuring protein expression by IHC and gene expression/pathway analysis by mRNA-sequencing. Drug efficacy studies were run with representative xenografts using the approved drug cetuximab as well as the new PI3K inhibitor PX-866. Tumors maintained their original morphology, genetic profiles and drug susceptibilities through serial passaging. The genetic makeup of these tumors was consistent with known frequencies of TP53, PI3KCA, NOTCH1 and NOTCH2 mutations. Because the EGFR inhibitor cetuximab is a standard HNSCC therapy, we tested its efficacy and observed a wide spectrum of efficacy. Cetuximab-resistant strains had higher PI3K/Akt pathway gene expression and protein activation than cetuximab-sensitive strains. The PI3K inhibitor PX-866 had anti-tumor efficacy in HNSCC models with PIK3CA alterations. Finally, PI3K inhibition was effective in two cases with NOTCH1 inactivating mutations. In summary, we have developed an HNSCC model covering its clinical spectrum whose major genetic alterations and susceptibility to anticancer agents represent contemporary HNSCC. This model enables to prospectively test therapeutic-oriented hypotheses leading to personalized medicine.
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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.