New Strategies for Treatment of ALK-Rearranged Non―Small Cell Lung Cancers

• Published in: Clinical cancer research Vol. 17; no. 23; pp. 7213 - 7218
• Main Authors: SASAKI, Takaaki, JÄNNE, Pasi A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-12-2011
• Subjects: Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Drug Resistance, Neoplasm - genetics; Humans; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Medical sciences; Pharmacology. Drug treatments; Pneumology; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - therapeutic use; Pyridines - therapeutic use; Receptor Protein-Tyrosine Kinases - antagonists & inhibitors; Receptor Protein-Tyrosine Kinases - genetics; Tumors of the respiratory system and mediastinum; Lung disease; Treatment; Respiratory disease; Lung cancer; C-Onc gene; Bronchus disease; Malignant tumor; non-small cell lung carcinoma; Anaplastic lymphoma kinase; Protooncogene; Research and development; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-11-1404

The identification of oncogenic alterations in subsets of patients with non-small cell lung cancer (NSCLC) is transforming clinical care. Genomic rearrangements in anaplastic lymphoma kinase (ALK) are detected in 3% to 7% of patients with NSCLC. The ALK tyrosine kinase inhibitor crizotinib has demonstrated clinical efficacy in ALK-rearranged NSCLC patients and was recently approved by the U.S. Food and Drug Administration. Crizotinib is currently under additional phase III clinical development as both initial and second-line therapy for advanced ALK-rearranged NSCLC. However, new challenges in the diagnosis and treatment of this subset of NSCLC have emerged, including the need to determine the most effective means of diagnosing ALK-rearranged NSCLC and the emergence of acquired drug resistance to crizotinib. In this review, we discuss current strategies for treatment and diagnosis, as well as the current knowledge about mechanisms of acquired resistance to crizotinib. Finally, we discuss the strategies that are underway to clinically overcome acquired drug resistance.