ArticleOtorhinolaryngology-head and neck surgery2016
Differential compensation mechanisms define resistance to PI3K inhibitors in
Article in Otorhinolaryngology-head and neck surgery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- CRISPR Screens Identify PIK3C2A as a Novel Mediator of EGFR Inhibitor Resistance in Head and Neck Squamous Cell Carcinoma.Head & neck · 2026Article
- Multi-kinase compensation rescues EGFR knockout in a cell line model of head and neck squamous cell carcinoma.Archives of oral biology · 2023Article
- Genome-wide open reading frame profiling identifies fibroblast growth factor signaling as a driver of PD-L1 expression in head and neck squamous cell carcinoma.Oral oncology · 2023Article
- Review
- Article
- Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.Head & neck · 2022Article
- PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient Survival.Cancers · 2022Article
- IGF2 Mediates Resistance to Isoform-Selective-Inhibitors of the PI3K in HPV Positive Head and Neck Cancer.Cancers · 2021Article
- Identification of PIK3CA multigene mutation patterns associated with superior prognosis in stomach cancer.BMC cancer · 2021Article
- Dacomitinib and gedatolisib in combination with fractionated radiation in head and neck cancer.Clinical and translational radiation oncology · 2021Article
- HS-173, a selective PI3K inhibitor, induces cell death in head and neck squamous cell carcinoma cell lines.Wiener klinische Wochenschrift · 2021Article
- The influence of PI3K inhibition on the radiotherapy response of head and neck cancer cells.Scientific reports · 2020Article
- Rationale for Using Irreversible Epidermal Growth Factor Receptor Inhibitors in Combination with Phosphatidylinositol 3-Kinase Inhibitors for Advanced Head and Neck Squamous Cell Carcinoma.Molecular pharmacology · 2019Article
- The genomic landscape of UM-SCC oral cavity squamous cell carcinoma cell lines.Oral oncology · 2018Article
- Leveraging Genomics for Head and Neck Cancer Treatment.Journal of dental research · 2018Review
- Article
- Novel DNA targeted therapies for head and neck cancers: clinical potential and biomarkers.Oncotarget · 2017Review
- ZAP70 Activation Compensates for Loss of Class IA PI3K Isoforms Through Activation of the JAK-STAT3 Pathway.Cancer diagnosis & prognosisArticle
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
objectiveRecent sequencing studies of head and neck squamous cell carcinomas (HNSCCs) have identified the phosphatidylinositol 3-kinase (PI3K) pathway as the most frequently mutated, oncogenic pathway in this cancer type. Despite the frequency of activating genomic alterations in PIK3CA (the gene encoding the catalytic subunit of PI3K, targeted inhibitors of PI3K have not shown clinical efficacy as monotherapies. We hypothesized that co-dependent pathways, including the Ras-MEK-ERK pathway, may still be functional in the presence of PI3K inhibitors and might serve as mediators of this resistance.
methodsWe assessed the hypothesis using resazurin cell viability and trypan blue exclusion assays. We also used Western blot to characterize Ras-MEK-ERK pathway activity. STUDY
designWe evaluated this hypothesis in six PIK3CA-amplified, PI3K inhibitor-resistant HNSCC cell lines following treatment with pan and alpha-isoform selective PI3K inhibitors (BKM120 and HS-173 respectively). We also tested the effect of combination treatment with PI3K inhibitor HS-173 and MEK inhibitor trametinib or EGFR inhibitor gefitinib.
resultsOur results displayed maintenance of Ras-MEK-ERK pathway activity in 4 of 6 HNSCC cell lines after PI3K inhibitor treatment. We also found that UM-SCC-69 and UM-SCC-108 cells display synergistic responses to dual therapy.
conclusionThis study suggests that inhibition of the PI3K and Ras-MEK-ERK pathways might be effective in some HNSCC patients; however, it also prompts the study of additional resistance mechanisms to identify synergistic combination therapies for tumors resistant to these di-therapies.
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