Introduction: ALK fusion gene is found in 3-5% of NSCLC patients. As the resultant ALK fusion protein constitutively activates ALK tyrosine kinase that causes tumorigenesis, ALK tyrosine kinase inhibitors have been developed for the treatment of ALK rearranged cancer and currently five ALK-TKIs have been clinically applied. Now, alectinib is widely used in first-line therapy. However, most of the patients experience the emergence of alectinib resistance due to the secondary mutation in ALK kinase domain such as I1171N or G1202R. Lorlatinib, third generation ALK-TKI, has shown to be able to overcome any of the earlier generation ALK-TKI resistant single point mutants including G1202R and I1171N. Conclusion: Our results imply that the clinical sequences after lorlatinib resistance using biopsy or liquid-biopsy might provide important information to choose the effective sequential ALK-TKI therapy. Further studies are still needed to uncover the unidentified lorlatinib resistance mechanisms. READ ARTICLE
Molecular Targets and Cancer Therapeutics DOI:10.1158/1535-7163.TARG-19-A125
Authors: Koutaroh Okada, Mitsugu Araki, Tomoko Oh-hara, Makoto Nishio, Yasushi Okuno, Naoya Fujita and Ryohei Katayama