Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Curr Oncol. 2022 Oct 16;29(10):7816-7831. doi: 10.3390/curroncol29100618.
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and is the leading cause of cancer-related death. Despite advances in chemotherapy and immunotherapy, the prognosis for advanced patients remains poor. The discovery of oncogenic driver mutations, such as anaplastic lymphoma kinase (ALK) mutations, means that a subset of patients has opportunities for targeted therapy. With the improvement of genetic testing coverage, more and more ALK fusion subtypes and ALK partners have been discovered, and more than 90 rare ALK fusion subtypes have been found in NSCLC. However, unlike the common fusion, echinoderm microtubule-associated protein-like 4 (EML4)-ALK, some rare ALK fusions such as striatin (STRN)-ALK and huntingtin interacting protein 1 (HIP1)-ALK, etc., the large-scale clinical data related to its efficacy are still immature. The clinical application of ALK-tyrosine kinase inhibitors (ALK-TKIs) mainly depends on the positivity of the ALK gene, regardless of the molecular characteristics of the fusion partner. Recent clinical studies in the ALK-positive NSCLC population have demonstrated differences in progression-free survival (PFS) among patients based on different ALK fusion subtypes. This article will introduce the biological characteristics of ALK fusion kinase and common detection methods of ALK fusion and focus on summarizing the differential responses of several rare ALK fusions to ALK-TKIs, and propose corresponding treatment strategies, so as to better guide the application of ALK-TKIs in rare ALK fusion population.
非小细胞肺癌（NSCLC）约占所有肺癌病例的 85%，是癌症相关死亡的主要原因。尽管化疗和免疫疗法取得了进展，但晚期患者的预后仍然较差。致癌驱动基因突变的发现，如间变性淋巴瘤激酶（ALK）突变，意味着一部分患者有机会进行靶向治疗。随着基因检测覆盖范围的提高，越来越多的 ALK 融合亚型和 ALK 伙伴被发现，在 NSCLC 中已经发现了超过 90 种罕见的 ALK 融合亚型。然而，与常见的融合（如棘皮动物微管相关蛋白样 4（EML4）-ALK）不同，一些罕见的 ALK 融合，如 striatin（STRN）-ALK 和 huntingtin 相互作用蛋白 1（HIP1）-ALK 等，其疗效相关的大规模临床数据仍不成熟。ALK 酪氨酸激酶抑制剂（ALK-TKIs）的临床应用主要依赖于 ALK 基因的阳性，而不考虑融合伙伴的分子特征。最近在 ALK 阳性 NSCLC 人群中的临床研究表明，基于不同的 ALK 融合亚型，患者的无进展生存期（PFS）存在差异。本文将介绍 ALK 融合激酶的生物学特性和 ALK 融合的常见检测方法，并重点总结几种罕见 ALK 融合对 ALK-TKIs 的差异化反应，提出相应的治疗策略，以便更好地指导 ALK-TKIs 在罕见 ALK 融合人群中的应用。
