학술논문

Current Status of Targeted Therapy for Anaplastic Lymphoma Kinase-Rearranged Non-Small Cell Lung Cancer
Document Type
Academic Journal
Source
Clinical Pharmacology & Therapeutics. Jan 01, 2014 95(1):15-23
Subject
Language
English
ISSN
0009-9236
Abstract
The identification of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in ~3–5% of non-small cell lung cancer (NSCLC) tissues and the demonstration that the first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC. Single-arm studies demonstrating rapid and durable responses in the majority of ALK-positive NSCLC patients treated with crizotinib have been followed by a randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients. However, despite the initial responses, most patients develop acquired resistance to crizotinib. Several novel therapeutic approaches targeting ALK-positive NSCLC are currently under evaluation in clinical trials, including second-generation ALK inhibitors, such as LDK378, CH5424802 (RO5424802802), and AP26113, and heat shock protein 90 inhibitors.