Zeng Zhu, Wang Tao, He Junjun, Wang Yuehong
Department of Respiratory Diseases, Thoracic Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of R&D, Hangzhou Repugene Technology Co., Ltd., Hangzhou, China.
Front Oncol. 2022 Oct 31;12:1010084. doi: 10.3389/fonc.2022.1010084. eCollection 2022.
We report a case with a novel and dual fusion that might be a delicate mechanism for the acquired resistance of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI). A patient with L858R lung adenocarcinoma developed disease progression after 72.7 months of gefitinib therapy; rebiopsy was done, and next-generation sequencing showed the disappearance of the previous mutations. In addition, two new fusions emerged, indicating that the emergence of dual ALK rearrangement may be the underlying mechanism of gefitinib resistance. The patient exhibits an excellent response to second-line alectinib treatment with a significant clinical benefit and a high quality of life. Finally, we summarized previous studies in which fusion is a required resistance mechanism to EGFR-TKI.
我们报告了一例具有新型双重融合的病例，这可能是表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）获得性耐药的一种微妙机制。一名患有L858R肺腺癌的患者在接受吉非替尼治疗72.7个月后出现疾病进展；进行了再次活检，下一代测序显示先前的突变消失。此外，出现了两种新的融合，表明双重ALK重排的出现可能是吉非替尼耐药的潜在机制。该患者对二线阿来替尼治疗表现出良好反应，具有显著的临床获益和较高的生活质量。最后，我们总结了先前的研究，其中融合是EGFR-TKI耐药的必要机制。
