Xue Yinyin, Li Wen, Li Pengfei, Huang Kaili, Zhou Qinghua, Wu Qiang
Department of Radiation Oncology Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Pharmacol. 2025 Mar 10;16:1489696. doi: 10.3389/fphar.2025.1489696. eCollection 2025.
The MET proto-oncogene (MET) plays a crucial role as an oncogenic driver gene in non-small cell lung cancer (NSCLC). At present, numerous types of MET exon 14 (METex14) skipping mutation have been identified, but different splice variants often exhibit varying treatment responses. There is currently no standardized treatment approach for rare METex14 mutation after resistance to epidermal growth factor receptor tyrosine kinases inhibitor (EGFR-TKI). Herein, we present for the first time a case of advanced lung adenocarcinoma with a novel METex14 skipping mutation following resistance to EGFR-TKI and subsequent sensitivity to savolitinib. In addition, the patient developed a novel METex14 skipping mutation after EGFR-TKI resistance, which we suspect may be a potential new mechanism of EGFR-TKI resistance that has not been reported.
We conducted surgical specimen pathology diagnosis and next-generation sequencing (NGS) of peripheral blood to ascertain the patient's pathological and molecular characteristics.
NGS testing identified a novel METex14 (c.2888-23_2888-8del) skipping mutation in the patient with advanced lung adenocarcinoma who developed resistance to EGFR-TKI, suggesting its potential involvement as one of the mechanisms underlying the resistance to EGFR-TKI. Following administration of savolitinib with a daily dose of 400 mg, the patient exhibited a partial response and achieved progression-free survival (PFS) exceeding 8 months.
The case presents a novel METex14 skipping mutation that emerges subsequent to the progression of advanced lung adenocarcinoma following EGFR-TKI treatment. Importantly, this mutation may serve as one of the mechanisms contributing to resistance against EGFR-TKI and exhibit sensitivity towards savolitinib treatment, providing reference for future similar cases in terms of treatment options.
MET原癌基因（MET）在非小细胞肺癌（NSCLC）中作为致癌驱动基因发挥着关键作用。目前，已鉴定出多种MET外显子14（METex14）跳跃突变，但不同的剪接变体往往表现出不同的治疗反应。对于表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）耐药后的罕见METex14突变，目前尚无标准化的治疗方法。在此，我们首次报告1例晚期肺腺癌患者，在对EGFR-TKI耐药后出现新的METex14跳跃突变，并对赛沃替尼敏感。此外，该患者在EGFR-TKI耐药后出现了新的METex14跳跃突变，我们怀疑这可能是尚未报道的EGFR-TKI耐药的潜在新机制。
我们进行了手术标本病理诊断及外周血二代测序（NGS），以确定患者的病理和分子特征。
NGS检测在1例对EGFR-TKI耐药的晚期肺腺癌患者中发现了新的METex14（c.2888-23_2888-8del）跳跃突变，提示其可能是EGFR-TKI耐药的潜在机制之一。给予患者每日400 mg赛沃替尼治疗后，患者出现部分缓解，无进展生存期（PFS）超过8个月。
该病例呈现了1例在EGFR-TKI治疗的晚期肺腺癌进展后出现的新的METex14跳跃突变。重要的是，该突变可能是导致EGFR-TKI耐药的机制之一，且对赛沃替尼治疗敏感，为未来类似病例的治疗选择提供了参考。
