Anaplastic lymphoma kinase rearrangement in lung Cancer: Its biological and clinical significance

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