ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2014
Blocking the PI3K pathway enhances the efficacy of ALK-targeted therapy in EML4-ALK-positive nonsmall-cell lung cancer.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- The novel ALK K1150dup mutation mediates resistance to frontline lorlatinib and retains sensitivity to gilteritinib.NPJ precision oncology · 2026Article
- RNase1-driven ALK-activation is an oncogenic driver and therapeutic target in non-small cell lung cancer.Signal transduction and targeted therapy · 2025Article
- Article
- Efficacy of alectinib in lung adenocarcinoma patients with different anaplastic lymphoma kinase (Translational lung cancer research · 2023Article
- EML4-ALK biology and drug resistance in non-small cell lung cancer: a new phase of discoveries.Molecular oncology · 2023Review
- ALK-positive lung cancer: a moving target.Nature cancer · 2023Review
- EML4-ALK fusion gene in non-small cell lung cancer.Oncology letters · 2022Review
- Alternative Treatment Options to ALK Inhibitor Monotherapy for EML4-ALK-Driven Lung Cancer.Cancers · 2022Review
- SPP1 overexpression is associated with poor outcomes in ALK fusion lung cancer patients without receiving targeted therapy.Scientific reports · 2021Article
- Concomitant mutation status ofTranslational lung cancer research · 2021Article
- Brain Metastases in Lung Cancers with Emerging Targetable Fusion Drivers.International journal of molecular sciences · 2020Review
- PI3K/AKT inhibition induces compensatory activation of the MET/STAT3 pathway in non-small cell lung cancer.Oncology letters · 2018Article
- An analysis of the gene interaction networks identifying the role of PARP1 in metastasis of non-small cell lung cancer.Oncotarget · 2017Article
- MicroRNA-588 suppresses tumor cell migration and invasion by targeting GRN in lung squamous cell carcinoma.Molecular medicine reports · 2016Article
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted therapy based on ALK tyrosine kinase inhibitors (ALK-TKIs) has made significant achievements in individuals with EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) fusion positive nonsmall-cell lung cancer (NSCLC). However, a high fraction of patients receive inferior clinical response to such treatment in the initial therapy, and the exact mechanisms underlying this process need to be further investigated. In this study, we revealed a persistently activated PI3K/AKT signaling that mediates the drug ineffectiveness. We found that genetic or pharmacological inhibition of ALK markedly abrogated phosphorylated STAT3 and ERK, but it failed to suppress AKT activity or induce apoptosis, in EML4-ALK-positive H2228 cells. Furthermore, targeted RNA interference of PI3K pathway components restored sensitivity to TAE684 treatment at least partially due to increased apoptosis. Combined TAE684 with PI3K inhibitor synergistically inhibited the proliferation of EML4-ALK-positive cells in vitro and significantly suppressed the growth of H2228 xenografts in vivo, suggesting the potential clinical application of such combinatorial therapy regimens in patients with EML4-ALK positive lung cancer.
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