2007年首次报道了伴有间变性淋巴瘤激酶重排(ALK)的非小细胞肺癌(NSCLC)。ALK重排的NSCLC约占NSCLC的3-8%。ALK重排的晚期NSCLC的一线治疗是靶向ALK的酪氨酸激酶抑制剂(TKI)。随着克唑替尼的发展,第一个ALK-TKI,患者的预后有了很大的改善。目前,FDA批准了五个TKIs。此外,新型TKI的临床试验,ensartinib,以及用于复合ALK突变的第四代ALK-TKI正在进行中。血管生成抑制剂和免疫检查点抑制剂的治疗也在研究中。然而,随着疾病的进展,癌症往往会产生抗性机制。除了ALK突变,其他机制,包括旁路信号通路的激活和组织学转化,造成阻力,这些机制的鉴定对于选择后续治疗很重要。已经报道了对组织和液体活检的研究,并有望成为识别耐药机制的有用工具。本手稿的目的是提供有关ALK-TKIs最近临床试验的信息,血管生成抑制剂,免疫检查点抑制剂,和化疗来描述组织和液体活检作为一种研究ALK-TKIs耐药机制的方法,并提出了一种拟议的治疗算法。
Non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase rearrangement (ALK) was first reported in 2007. ALK-rearranged NSCLC accounts for about 3-8% of NSCLC. The first-line therapy for ALK-rearranged advanced NSCLC is tyrosine kinase inhibitors (TKI) targeting ALK. Following the development of crizotinib, the first ALK-TKI, patient prognosis has been greatly improved. Currently, five TKIs are approved by the FDA. In addition, clinical trials of the novel TKI, ensartinib, and fourth-generation ALK-TKI for compound ALK mutation are ongoing. Treatment with angiogenesis inhibitors and immune checkpoint inhibitors is also being studied. However, as the disease progresses, cancers tend to develop resistance mechanisms. In addition to ALK mutations, other mechanisms, including the activation of bypass signaling pathways and histological transformation, cause resistance, and the identification of these mechanisms is important in selecting subsequent therapy. Studies on tissue and liquid biopsy have been reported and are expected to be useful tools for identifying resistance mechanisms. The purpose of this manuscript is to provide information on the recent clinical trials of ALK-TKIs, angiogenesis inhibitors, immune checkpoint inhibitors, and chemotherapy to describe tissue and liquid biopsy as a method to investigate the mechanisms of resistance against ALK-TKIs and suggest a proposed treatment algorithm.