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Current Status of Targeted Therapy for Anaplastic Lymphoma Kinase–Rearranged Non–Small Cell Lung Cancer
Author(s) -
Solomon B,
Wilner KD,
Shaw AT
Publication year - 2014
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2013.200
Subject(s) - crizotinib , anaplastic lymphoma kinase , medicine , lung cancer , alk inhibitor , oncology , targeted therapy , cancer research , tyrosine kinase , tyrosine kinase inhibitor , chemotherapy , cancer , receptor , malignant pleural effusion
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. Clinical Pharmacology & Therapeutics (2013); 95 1, 15–23 advance online publication 13 November 2013. doi: 10.1038/clpt.2013.200