Respiratory investigation
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Respiratory investigation · Nov 2014
ReviewAnaplastic lymphoma kinase rearrangement in lung cancer: its biological and clinical significance.
Anaplastic lymphoma kinase (ALK) has been found to fuse with other partners, such as echinoderm microtubule-associated protein-like 4 (EML4), leading to potent malignant transformation in lung cancer, specifically non-small-cell lung cancer (NSCLC). The frequency of the ALK rearrangement in patients with NSCLC is reported to be 4-7%, and the rearrangement is frequently observed in relatively younger patients, non- or light smokers and those with adenocarcinoma histology without other genetic disorders, such as mutations of the epidermal growth factor receptor gene. Crizotinib, which is a first-in-class ALK tyrosine kinase inhibitor (TKI), was shown to be effective and well tolerated in ALK-positive NSCLC patients by a single-arm phase I study. ⋯ However, the mechanisms of resistance to crizotinib are major concerns when administering crizotinib to ALK-positive NSCLC patients, and they include second mutations and a gain in the copy number of the ALK gene, activation of other oncogenes, etc. Treatment strategies to overcome these mechanisms of resistance have been developed, including the use of second-generation ALK inhibitors, such as alectinib and ceritinib, heat shock protein 90 inhibitors and so on. In this article, we review the pre-clinical and clinical data regarding the biologal and clinical significance of the ALK rearrangement in lung cancer.