约 3-5% 的非小细胞肺癌 (NSCLC) 中发现了间变性淋巴瘤激酶 (ALK) 基因重排，ALK 重排 NSCLC 被认为是一种具有独特临床特征的癌基因成瘾性癌症。 几种 ALK 抑制剂已被研究并批准用于治疗晚期 ALK 重排 NSCLC，与化疗相比，其在疗效和安全性方面具有优越性。第二代和第三代 ALK 抑制剂（alectinib、brigatinib 和 lorlatinib）为 NSCLC 患者提供了具有临床意义的生存期延长和非常好的生活质量。然而，对这些药物的耐药性总是会发生，二线治疗的选择不太令人满意。这些药物之间无法进行直接比较，并且选择布加替尼、艾来替尼和劳拉替尼作为一线治疗仍然具有挑战性。最近，在切除的 IB-IIIA 期 ALK 重排 NSCLC 中，艾来替尼已被证明与化疗相比可以改善疗效，将 ALK 抑制剂提供的临床益处扩展到辅助治疗。 ALK 抑制剂在 NSCLC 治疗中的未来发展包括寻找一线治疗获得性耐药的最佳管理方法，并将 ALK 抑制剂的使用扩展到新辅助治疗，最好是围手术期治疗。

Anaplastic lymphoma kinase (ALK) gene-rearrangements are identified in about 3-5% of non-small cell lung cancers (NSCLC), and ALK-rearranged NSCLC is to be considered an oncogene-addicted cancer with peculiar clinical characteristics.Several ALK inhibitors have been studied and approved for use in the treatment of advanced ALK-rearranged NSCLC with reported superiority in terms of efficacy and safety profile compared with chemotherapy. Second- and third-generation ALK inhibitors (alectinib, brigatinib, and lorlatinib) offer to NSCLC patients a clinically meaningful prolongment of survival with a very good quality of life profile. However, resistances to these agents always occur, with less satisfying options for second-line treatments. Direct comparisons among these agents are not available, and the choice among brigatinib, alectinib, and lorlatinib as first-line treatment remains challenging. Very recently, alectinib has been demonstrated to improve efficacy outcomes compared with chemotherapy also in resected stage IB-IIIA ALK-rearranged NSCLC, extending the clinical benefit offered by ALK inhibitors also to the adjuvant setting.Future development of ALK inhibitors in NSCLC treatment includes the search for optimal management of acquired resistance to first-line treatments and the extension of use of ALK inhibitors also to neoadjuvant and preferably to perioperative setting.