Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

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.


Tumour Angiogenesis Regulation by the miR-200 Family

We demonstrate a difference in clinical outcome based on miR-200’s role in blocking tumour angiogenesis. We demonstrate that miR-200 inhibits angiogenesis through direct and indirect mechanisms by targeting interleukin-8 and CXCL1 secreted by the tumour endothelial and cancer cells. Delivery of miR-200 members into the tumour endothelium resulted in marked reductions in metastasis and angiogenesis, and induced vascular normalization.


Vimentin expression predicts the occurrence of metastases in non small cell lung carcinomas

Epithelial-to-mesenchymal transition (EMT) is believed to contribute to tumour invasion. Vimentin expression by carcinoma cells is a largely recognized marker of EMT. This study aimed at examining vimentin expression in non small cell lung carcinomas (NSCLC).

Our data demonstrate that vimentin expression is a frequent event in NSCLC and that its expression can be associated with a lack of differentiation and the occurrence of metastases.