Suda Kenichi, Mitsudomi Tetsuya
Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Transl Lung Cancer Res. 2020 Dec;9(6):2618-2628. doi: 10.21037/tlcr-20-186.
Recent evidence has shown that gene fusions caused by chromosomal rearrangements are frequent events in the initiation and during progression of solid tumors, including non-small cell lung cancers (NSCLCs). Since the discoveries of and fusions in 2007 and the subsequent successes of pharmacological targeting for these fusions, numerous efforts have identified additional oncogenic driver fusions in NSCLCs, especially in lung adenocarcinomas. In this review, we will summarize recent advances in this field focusing on novel oncogenic fusions other than , , , and fusions, which are summarized in other articles in this thematic issue. These novel gene fusions include () fusions, fusions, fusion genes involving () family members, fusions, and other rare fusions. In addition, evidence has suggested that acquisition of gene fusions by cancer cells can be a molecular mechanism of acquired resistance to targeted therapies. Most of the current data are from analyses of resistance mechanisms to EGFR tyrosine kinase inhibitors in lung cancers with oncogenic mutations. However, a few recent studies suggest that gene fusions can also be a resistance mechanism to -tyrosine kinase inhibitors in lung cancers with oncogenic fusions. Detection, validation, and pharmacological inhibition of these fusion genes are becoming more important in the treatment of NSCLC patients.
最近的证据表明，染色体重排导致的基因融合在实体瘤（包括非小细胞肺癌，NSCLC）的发生和进展过程中是常见事件。自2007年发现 融合基因以及随后针对这些融合基因的药物靶向治疗取得成功以来，众多研究致力于在NSCLC中，尤其是肺腺癌中，鉴定出更多致癌驱动融合基因。在本综述中，我们将总结该领域的最新进展，重点关注除 、 、 、 融合基因之外的新型致癌融合基因，这些融合基因在本期专题的其他文章中有总结。这些新型基因融合包括 （）融合、 融合、涉及 （）家族成员的融合基因、 融合以及其他罕见融合。此外，有证据表明癌细胞获得基因融合可能是获得性靶向治疗耐药的分子机制。目前的大多数数据来自对具有致癌 突变的肺癌中表皮生长因子受体（EGFR）酪氨酸激酶抑制剂耐药机制的分析。然而，最近的一些研究表明，基因融合在具有致癌 融合的肺癌中也可能是对 -酪氨酸激酶抑制剂的耐药机制。这些融合基因的检测、验证和药物抑制在NSCLC患者的治疗中变得越来越重要。
