ALK（anaplastic lymphoma kinase）抑制劑在有ALK融合蛋白表現肺癌病人的治療

ALK (anaplastic lymphoma kinase) Inhibitors in Lung Cancer Patients with ALK Fusion Protein

有ALK（anaplastic lymphoma kinase）基因重組之肺癌在非小細胞肺癌佔的比例約4-8%，就像表皮生因子受體（EGFR）突變一樣，ALK基因重組蛋白具有致癌驅動蛋白的特性造成癌細胞過度依賴此腫瘤蛋白，使得ALK抑制劑可非常有效的抑制ALK基因重組陽性細胞的生長。雖然第一代ALK抑制劑crizotinib臨床上治療ALK陽性非小細胞肺癌有顯著療效，但在接受一段時間的治療後會產生抗藥性。新一代的ALK抑制劑能有效對抗ALK其因突變與拷貝數增加造成的抗藥性，如ceritinib與alectinib等，在臨床上對於原生的ALK基因重組以及對crizotinib產生抗藥性的腫瘤都可以有抑制的效果。

ALK (anaplastic lymphoma kinase) rearrangements in non-small-cell lung cancer (NSCLC) have an estimated prevalence of 4-8%. ALK fusion proteins undergo ligand-independent dimerization and result in constitutive activation of the ALK tyrosine kinase. Tyrosine-kinase inhibitors that target the kinase activity of ALK have been found to have significant antiproliferative and proapoptotic effects. Although crizotinib treatment in ALK rearrangement-positive patients yields a pronounced clinical improvement, almost all patients eventually develop drug resistance. Ceritinib and alectinib are the new generation of ALK inhibitors, which overcome crizotinib resistance arising from ALK mutations or amplification. Other resistant mechanisms, such as activation of alternative pathways, remain to be discovered and validated. Further development of treatment strategy will improve the clinical outcome of patients with ALK-positive advanced NSCLC.