Abstract
Although patients with ALK-positive non-small cell lung cancer (NSCLC) are initially effective on treatment with ALK tyrosine kinase inhibitors (TKIs), resistance will inevitably develop. Of these patients, 2/3 will develop ALK-independent resistance and little is known about the mechanisms of ALK-independent resistance. In pre-clinical studies, the activation of several bypass signaling pathways has been implicated in the development of resistance, including the MET, EGFR, SRC and IGF1R pathways. Among these, the MET pathway is one of the signaling pathways that has recently been extensively studied, and activation of this pathway is one of the mechanisms of ALK-independent drug resistance. Here, we report a successful case of an advanced NSCLC patient who was resistant to treatment with ALK TKIs and developed MET amplification, who achieved 23 months of progression-free survival after post-line treatment with ensartinib.