EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

ALK gene fusion occurs in approximately 3-7% of non-small cell lung cancer (NSCLC). For patients with ALK positive NCSLC, crizotinib and ceritinib are FDA approved ALK inhibitors, however, patients inevitably acquire resistance to such therapies typically within one to two years. Interrogation of in vitro ALK-positive NSCLC cell line models of acquired resistance to first and second-generation ALK inhibitors revealed acquired epithelial-to-mesenchymal transition (EMT) mechanisms. Here we demonstrated that knockdown of upregulated mesenchymal markers in acquired resistant lines decreased the invasive and migratory capabilities of the cells, however, it did not restore sensitivity to ALK inhibitors.

Source: Molecular Oncology - November 19, 2015 Category: Cancer & Oncology Authors: Arjan Gower, Wei-Hsun Hsu, Shuo-Tse Hsu, Yisong Wang, Giuseppe Giaccone Source Type: research