Moreover, previous studies have shown that Pg extracts decrease inflammation in lung cancer cell lines by inhibiting phosphatidylinositol-3,4,5-trisphosphate (PI3K)-dependent phosphorylation of AKT in vitro and inhibiting the activation of NF-kB in vivo.
Here, we focused on Akt kinase-interacting protein1 (Aki1), a scaffold protein of PI3K (phosphoinositide 3-kinase)/PDK1 (3-phosphoinositide-dependent protein kinase)/Akt that determines receptor signal selectivity for non-mutated EGFR, and assessed its role in EGFR mutant lung cancer with or without gatekeeper T790M mutation.
In this study, we investigated the potential of targeting the catalytic class I(A) PI3K isoforms in small cell lung cancer (SCLC), which is the most aggressive of all lung cancer types.
Using the DNA extracted from formalin-fixed paraffin-embedded tumor samples, a MassArray-based Lung Cancer Mutations Screening Panel was performed to test for 179 individual mutations in 10 genes, including EGFR, KRAS, BRAF, ERBB2, JAK2, AKT1, AKT2, KIT, MET and PIK3CA, which have been implicated in lung carcinogenesis and/or considered as potential therapeutic targets.
This work sheds light on the ability of RASto activate PI3K through direct interaction, indicating that input is also required from a receptor tyrosinekinase, IGF1R in the case of KRAS -mutant lung cancer.
A detailed immunohistochemical analysis of the PI3K/AKT/mTOR pathway in lung cancer: correlation with PIK3CA, AKT1, K-RAS or PTEN mutational status and clinicopathological features.
This study demonstrated elevated levels of MARCKS and phospho-MARCKS in highly invasive lung cancer cell lines and lung cancer specimens from non-small-cell lung cancer patients. siRNA knockdown of MARCKS expression in these highly invasive lung cancer cell lines reduced cell migration and suppressed PI3K (phosphatidylinositol 3'-kinase)/Akt phosphorylation and Slug level.
Our analysis also highlighted the potential of these LC-miRNAs to regulate the cell differentiation, proliferation, endocytosis and migration signaling logically required to cause an LC cell mainly through five canonical pathways (PI3K-Akt signaling pathway, pathways in cancer, MAPK signaling pathway, HTLV-I infection and focal adhesion).
In this issue of Cancer Cell, Castellano and colleagues report that KRAS-driven lung cancers require the Ras-p110α interaction for full activation of PI3K and tumor maintenance.
A patient with metastatic lung adenocarcinoma harboring concurrent EGFR L858R, EGFR germline T790M, and PIK3CA mutations: the challenge of interpreting results of comprehensive mutational testing in lung cancer.
Ectopic expression of CD74-NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar.
PIK3CA gene encoding a catalytic subunit of the phosphatidylinositol-3-kinase (PI3K) is mutated and/or amplified in various neoplasia, including lung cancer.
Also, KPT-330 was effective even against NSCLC cells with a transforming mutation of either exon 20 of EGFR, TP53, phosphatase and tensin homologue, RAS or PIK3CA, suggesting the drug might be effective against a variety of lung cancers irrespective of their driver mutation.
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.