Second-generation anaplastic lymphoma kinase inhibitors: revolutionary or evolutionary?

Since the discovery of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) in 2007 (1), crizotinib was developed as the first targeted therapy for patients with advanced or metastatic ALK-positive NSCLC (2). However, even though the dramatic and rapid response, most patients experienced disease progression within one year after commencement of crizotinib (3,4). To overcome crizotinib resistance, many next-generation ALK inhibitors have been developed.