ArticleBritish journal of cancer2012
Preclinical evaluation of dual PI3K-mTOR inhibitors and histone deacetylase inhibitors in head and neck squamous cell carcinoma.
Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 61 citations in OpenAlex.
- SOAR elucidates biological insights and empowers drug discovery through spatial transcriptomics.Science advances · 2025Article
- The Role of the PI3K/Akt/mTOR Axis in Head and Neck Squamous Cell Carcinoma.Biomedicines · 2024Review
- Targeted therapy for head and neck cancer: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Histone Deacetylase Inhibitors as Multitarget-Directed Epi-Drugs in Blocking PI3K Oncogenic Signaling: A Polypharmacology Approach.International journal of molecular sciences · 2020Review
- A PI3K/AKT Scaffolding Protein, IQ Motif-Containing GTPase Associating Protein 1 (IQGAP1), Promotes Head and Neck Carcinogenesis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Identification of Targetable Pathways in Oral Cancer Patients via Random Forest and Chemical Informatics.Cancer informatics · 2019Article
- The anti-tumor effects of dual PI3K/mTOR inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A on inducing autophagy in esophageal squamous cell carcinoma.Journal of Cancer · 2018Article
- PI3K/mTOR dual inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A synergistically exert anti-tumor activity in breast cancer.Oncotarget · 2017Article
- Molecular Aspects of Head and Neck Cancer Therapy.Hematology/oncology clinics of North America · 2015Review
- Review
- Histone Deacetylase Inhibitors Inhibit the Proliferation of Gallbladder Carcinoma Cells by Suppressing AKT/mTOR Signaling.PloS one · 2015Article
- A comprehensive evaluation of biomarkers predictive of response to PI3K inhibitors and of resistance mechanisms in head and neck squamous cell carcinoma.Molecular cancer therapeutics · 2014Article
- Oral epithelial stem cells - implications in normal development and cancer metastasis.Experimental cell research · 2014Review
- Human papillomavirus-associated adenocarcinoma of the base of tongue: potentially actionable genetic changes.Head and neck pathology · 2014Article
- mTORC1/C2 and pan-HDAC inhibitors synergistically impair breast cancer growth by convergent AKT and polysome inhibiting mechanisms.Breast cancer research and treatment · 2014Article
- Overcoming inherent resistance to histone deacetylase inhibitors in multiple myeloma cells by targeting pathways integral to the actin cytoskeleton.Cell death & disease · 2014Article
- Role of anoctamins in cancer and apoptosis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Review
- Optical metabolic imaging of treatment response in human head and neck squamous cell carcinoma.PloS one · 2014Article
- PIK3CA, HRAS and PTEN in human papillomavirus positive oropharyngeal squamous cell carcinoma.BMC cancer · 2013Article
- Sustained inhibition of deacetylases is required for the antitumor activity of the histone deactylase inhibitors panobinostat and vorinostat in models of colorectal cancer.Investigational new drugs · 2013Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe examine the potential value of a series of clinically relevant PI3K-mTOR inhibitors alone, or in combination with histone deacetylase inhibitors, in a model of head and neck squamous cell carcinoma (HNSCC).
methodsHead and neck squamous cell carcinoma cell lines, human keratinocyte and HNSCC xenograft models were treated with histone deacetylase inhibitors (HDACIs) and new generation PI3K and dual PI3K-mTOR inhibitors either alone or in combination. Cell and tumour tissue viability and proliferation were then determined in vitro and in vivo.
resultsPhosphatidylinositol-3-phosphate kinase, AKT and dual PI3K-mTOR inhibitors caused marked in vitro enhancement of cytotoxicity induced by HDACIs in HNSCC cancer cells. This effect correlates with AKT inhibition and is attenuated by expression of constitutively active AKT. Histone deacetylase inhibitor and phosphatidylinositol-3-phosphate kinase inhibitors (PI3KIs) inhibited tumour growth in xenograft models of HNSCC. Importantly, we observed intratumoural HDAC inhibition and PI3K inhibition as assessed by histone H3 acetylation status and phospho-AKT staining, respectively. However, we saw no evidence of improved efficacy with an HDACI/PI3KI combination.
interpretationThat PI3K and dual PI3K-mTOR inhibitors possess antitumour effect against HNSCC in vivo.
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