ALK rearrangement, most commonly EML4-ALK, is detected in approximately 3%–5% of NSCLC. ALK tyrosine kinase inhibitor (TKI), shows dramatic clinical efficacy, however, almost all patients acquire resistance over time. The most defined mechanism of crizotinib resistance is secondary ALK mutations. A recent study reported that epithelial-to-mesenchymal transition (EMT) and ALK resistance mutation were simultaneously detected in a single tumor lesion in patients with ALK-rearranged lung cancer who were resistant to ALK-TKIs. However, it is still unknown whether ALK-TKI resistant tumor cells combine mesenchymal phenotype with ALK resistance mutation, or each of the mesenchymal type tumor cells and ALK resistance mutation–positive cells coexist in a single lesion. In any of these cases, no therapy for EMT-associated targeted drug resistance has yet been established. Specimens from a patient with ALK-rearranged lung adenocarcinoma who acquired resistance to crizotinib were stained with IHC, ..... READ ARTICLE
Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1186
Authors: K. Fukuda, S. Takeuchi, S. Arai, S. Nanjo, R. Katayama, K. Takeuchi, M. Nishio, S. Yano