Implementation of precision medicine in lung cancer has benefited from intense research in the past years, developing subsequently an improved quality of life and increased overall survival of the patients. Targeted therapy has become one of the most important therapeutic innovations for the non-small cell lung cancer (NSCLC) category with anaplastic lymphoma kinase (ALK) gene rearrangement. The aim of this review is to provide a through overview of the main molecules of ALK tyrosine kinase inhibitors (TKI) with their general and particular mechanisms of resistance, the main methods of ALK gene detection, each with advantages and limits and the future perspectives currently under research which try to overcome the mechanisms of resistance. We have used two of the most reliable medical databases EMBASE and PubMed to properly select the latest and the most relevant articles for this topic. Encouraged by the promising results, the clinical practice was enriched by the approval of tyrosine kinase inhibitor molecules, three generations being developed, each one with more powerful agents than the previous ones. Unfortunately, the resistance to TKI eventually occurs and it may be induced by several mechanisms, either known or unknown. Crizotinib was the most intensely studied TKI , becoming the first molecule approved into clinical practice and although four other drugs have been broadly used (alectinib, ceritinib, brigatinib and lorlatinib) it seems that even the most recently developed one remains imperfect due to the resistance mutations that developed. There are two types of resistance generally described for the entire class and for the particular drugs, but half of them remain unknown.

中文翻译：

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对肺癌的洞察：探索 ALK TKI 和耐药机制的综合综述。

肺癌精准医疗的实施得益于过去几年的深入研究，随后提高了患者的生活质量并提高了总体生存率。靶向治疗已成为间变性淋巴瘤激酶 (ALK) 基因重排的非小细胞肺癌 (NSCLC) 类别最重要的治疗创新之一。本综述的目的是对 ALK 酪氨酸激酶抑制剂 (TKI) 的主要分子及其一般和特殊的耐药机制、ALK 基因检测的主要方法、各自的优势和局限性以及目前的未来展望进行全面概述。正在研究中，试图克服耐药机制。我们使用了两个最可靠的医学数据库 EMBASE 和 PubMed 来正确选择与该主题相关的最新和最相关的文章。受到有希望的结果的鼓舞，临床实践因酪氨酸激酶抑制剂分子的批准而丰富，正在开发三代，每一代都比以前的更强大。不幸的是，最终会出现对 TKI 的抗性，它可能是由几种已知或未知的机制引起的。克唑替尼是研究最深入的 TKI，成为第一个获准进入临床实践的分子，尽管其他四种药物已被广泛使用（艾乐替尼、色瑞替尼、布加替尼和劳拉替尼），但由于耐药性突变，即使是最近开发的药物似乎仍不完美开发的。