Treating patients with ALK-positive non-small cell lung cancer: latest evidence and management strategy.
Rearrangements in anaplastic lymphoma kinase (ALK) gene and echinoderm microtubule-associated protein-like 4 (EML4) gene were first described in a small portion of patients with non-small cell lung cancer (NSCLC) in 2007. Fluorescence in situ hybridization is used as the diagnostic test for detecting an EML4-ALK rearrangement. Crizotinib, an ALK inhibitor, is effective in treating advanced ALK-positive NSCLC, and the US Food and Drug Administration approved it for treating ALK-positive NSCLC in 2011. Several mechanisms of acquired resistance to crizotinib have recently been reported. Second-generation ALK inhibitors were designed to overcome these resistance mechanisms. Two of them, ceritinib and alectinib, were approved in 2014 for advanced ALK-positive NSCLC in the US and Japan, respectively. Heat shock protein 90 (Hsp90) inhibitors also showed activity against ALK-positive NSCLC. Here we review the recent development of crizotinib, ceritinib, alectinib and other second-generation ALK inhibitors as well as Hsp90 inhibitors. We also discuss management strategies for advanced ALK-positive NSCLC.
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Bin-Chi
BC
Liao
Department of Oncology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan.
Chia-Chi
CC
Lin
Department of Internal Medicine, National Taiwan University Hospital, Taiwan Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Jin-Yuan
JY
Shih
Department of Oncology, National Taiwan University Hospital, Taiwan Graduate Institute of Oncology and Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan.
James Chih-Hsin
JC
Yang
EML4–ALK rearrangement; alectinib; ceritinib; crizotinib; heat shock protein 90 inhibitor; non-small cell lung cancer