Anaplastic Lymphoma Kinase Inhibitors in Non-Small Cell Lung Cancer.

Abstract

Lung cancer is the leading cause of cancer death among both sexes in the United States and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Over the last several decades, there have been many advances in both surgical approaches and systemic therapies for the treatment of NSCLC, but the prognosis for advanced disease remains poor. New research, however, is exploring the use of targeted therapies for the treatment of NSCLC. The anaplastic lymphoma kinase (ALK) is involved in normal mammalian central nervous system development. A novel fusion gene involving ALK and the echinoderm microtubule-associated protein-like 4 (EML4) gene has been associated with approximately 5% of NSCLCs and is mutually exclusive of other oncogenic driver mutations. Targeted therapies against this ALK rearrangement are a relatively new treatment modality that aims to improve the prognosis of patients with late-stage disease. Two such drugs have Food and Drug Administration (FDA) approval currently: Crizotinib and Ceritinib. Many other ALK inhibitors are currently being studied in clinical trials as well. The authors aim to provide a comprehensive review of ALK inhibitors for use in NSCLC as well as the future directions and challenges to developing these targeted therapies.