ArticleOncotarget2017
Enhanced efficacy of AKT and FAK kinase combined inhibition in squamous cell lung carcinomas with stable reduction in PTEN.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Phase 2 study of the focal adhesion kinase inhibitor defactinib (VS-6063) in previously treated advanced KRAS mutant non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2020Trial
- ModularFrontiers in toxicology · 2026Article
- Article
- Targeting Signaling Excitability in Cervical and Pancreatic Cancer Cells Through Combined Inhibition of FAK and PI3K.International journal of molecular sciences · 2025Article
- Article
- Novel FAK inhibitors suppress tumor growth and reverse EGFR-TKI resistance in non-small cell lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Landscape of targeted therapies for lung squamous cell carcinoma.Frontiers in oncology · 2024Review
- PTEN Expression Was Significantly Associated with PD-L1 Score but Not with EBV Infection in Gastric Cancer.OncoTargets and therapy · 2022Article
- Article
- RGS12 Represses Oral Cancer via the Phosphorylation and SUMOylation of PTEN.Journal of dental research · 2021Article
- Focal adhesion kinase inhibition synergizes with nab-paclitaxel to target pancreatic ductal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2021Article
- Study and analysis of antitumor resistance mechanism of PD1/PD-L1 immune checkpoint blocker.Cancer medicine · 2020Review
- Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds.British journal of cancer · 2020Article
- PTEN Alterations as a Potential Mechanism for Tumor Cell Escape from PD-1/PD-L1 Inhibition.Cancers · 2019Review
- Blocking ROR1 enhances the roles of erlotinib in lung adenocarcinoma cell lines.Oncology letters · 2019Article
- RAC1 Takes the Lead in Solid Tumors.Cells · 2019Review
- Regulation of PTEN expression by noncoding RNAs.Journal of experimental & clinical cancer research : CR · 2018Review
- EYA2 promotes lung cancer cell proliferation by downregulating the expression of PTEN.Oncotarget · 2017Article
- New Treatment Opportunities in Phosphatase and Tensin Homolog (PTEN)-Deficient Tumors: Focus on PTEN/Focal Adhesion Kinase Pathway.Frontiers in oncology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Squamous cell lung carcinoma (SCC) accounts for 30% of patients with NSCLC and to date, no molecular targeted agents are approved for this type of tumor. However, recent studies have revealed several oncogenic mutations in SCC patients, including an alteration of the PI3K/AKT pathway, i.e. PI3K point mutations and amplification, AKT mutations and loss or reduced PTEN expression. Prompted by our observation of a correlation between PTEN loss and FAK phosphorylation in a cohort of patients with stage IV SCC, we evaluated the relevance of PTEN loss in cancer progression as well as the efficacy of a new combined treatment with the pan PI3K inhibitor buparlisip and the FAK inhibitor defactinib. An increase in AKT and FAK phosphorylation, associated with increased proliferation and invasiveness, paralleled by the acquisition of mesenchymal markers, and overexpression of the oncomir miR-21 were observed in SKMES-1-derived cell clones with a stable reduction of PTEN. Notably, the combined treatment induced a synergistic inhibition of cell proliferation, and a significant reduction in cell migration and invasion only in cells with reduced PTEN. The molecular mechanisms underlying these findings were unraveled using a specific RTK array that showed a reduction in phosphorylation of key kinases such as JNK, GSK-3 α/β, and AMPK-α2, due to the concomitant decrease in AKT and FAK activation. In conclusion, the combination of buparlisib and defactinib was effective against cells with reduced PTEN and warrants further studies as a novel therapeutic strategy for stage IV SCC patients with loss of PTEN expression.
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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.