ALECTINIB HYDROCHLORIDE ALK Receptor Tyrosine Kinase Inhibitor Oncolytic

作者：Cole P^*

来源：Drugs of the Future, 2013, 38(12): 799-805.

DOI：10.1358/dof.2013.38.12.2094760

• Anaplastic lymphoma kinase
• Anaplastic large cell lymphoma
• ALK tyrosine kinase receptor
• Oncolytic
• Alectinib hydrochloride
• AF-802

Alterations in the anaplastic lymphoma kinase (ALK) gene have been implicated in human cancers. Among these findings, the fusion gene comprising EML4 and ALK has been identified in non-small cell lung cancer (NSCLC) and fusion of ALK to NPM1 has been observed in anaplastic large cell lymphoma (ALCL). The possibility of targeting ALK in human cancer was advanced with the launch of crizotinib for NSCLC in the U. S. in 2011. The development of resistance to crizotinib in tumors, however, has led to the need for second-generation ALK inhibitors. One of these, alectinib hydrochloride, has been found to be an orally active, potent and highly selective ALK inhibitor with activity in ALK-driven tumor models. Alectinib has shown preclinical activity against cancers with ALK gene alterations, including NSCLC cells expressing the EML4ALK fusion and ALCL cells expressing the NPM-ALK fusion. Alectinib was well tolerated and active in a phase I/II study conducted in Japan in patients with ALK-rearranged advanced NSCLC and in patients with ALK-positive NSCLC who had progressed on crizotinib. Alectinib has been submitted for approval in Japan for the treatment of ALK fusion gene-positive NSCLC and is in phase I/II development for ALK-rearranged NSCLC in the U. S.

• 出版日期2013-12