CO-1686 is a novel, irreversible and orally delivered kinase inhibitor that specifically targets the mutant forms of EGFR including T790M while exhibiting minimal activity towards the wild-type (WT) receptor. Oral administration of CO-1686 as single agent induces tumor regression in EGFR mutated NSCLC tumor xenograft and transgenic models. In NSCLC cells with acquired resistance to CO-1686 in vitro, there was no evidence of additional mutations or amplification of the EGFR gene, but resistant cells exhibited signs of epithelial-mesenchymal transition (EMT) and demonstrated increased sensitivity to AKT inhibitors.
Epidermal growth factor receptor (EGFR) suppresses the maturation of specific tumour-suppressor-like miRNAs in response to hypoxic stress through phosphorylation of argonaute 2 (AGO2) at Tyr 393. The association between EGFR and AGO2 is enhanced by hypoxia, leading to elevated AGO2-Y393 phosphorylation, which in turn reduces the binding of Dicer to AGO2 and inhibits miRNA processing from precursor miRNAs to mature miRNAs.These findings suggest that modulation of miRNA biogenesis is important for stress response in tumour cells and has potential clinical implications.
We examined the impact of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) on progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients with and without EGFR mutations.
EGFR-TKIs therapy statistically significantly delays disease progression in EGFR mutation-positive (EGFRmut+) patients but has no demonstrable impact on OS. EGFR mutation is a predictive biomarker of PFS benefit with EGFR-TKIs treatment in all settings. These findings support EGFR mutation assessment before initiation of treatment. EGFR-TKIs should be considered as front-line therapy in EGFRmut+ advanced NSCLC patients.
Interstitial lung disease (ILD), especially idiopathic pulmonary fibrosis, has been shown to be associated with lung carcinogenesis. However, an association between epidermal growth factor receptor (EGFR) mutation status and preexisting ILD in patients with lung adenocarcinoma is unknown.
This study showed that patients with pulmonary adenocarcinoma and ILD had a lower probability of carrying tumor EGFR mutations.