PDF(Pubmed)
Abstract：
BRAF fusions are rare driver oncogenes in non-small cell lung cancer (NSCLC). Similar with BRAF V600E mutation, it could also activate the MAPK signaling pathway. There are a few case reports which had indicated the potential response to BRAF inhibitors and its important role as de novo driver mutation. In addition, the co-occurring MET amplification has been defined as a poor prognostic factor in patients with epidermal growth factor receptor (EGFR) mutant NSCLC. Currently, there are ongoing clinical trials which investigate the MET amplification as a therapeutic target in patients with EGFR mutant NSCLC and acquired resistance to osimertinib, which imply that the MET amplification also had a therapeutic significance. However, the co-occurring MET amplification had not been studied in patients with BRAF fusion before. A 67-year-old man was diagnosed with metastatic poorly-differentiated adenocarcinoma. He received first-line therapy with the combination of pembrolizumab and chemotherapy because the genomic test revealed wild-type EGFR, and negativity of ALK and ROS1 by immunohistochemical stain. Upon disease progression, the next-generation sequencing revealed co-occurring KIAA1549-BRAF fusion and MET amplification. Subsequent dabrafenib, trametinib, and capmatinib combination therapy showed a remarkable treatment effect. The combination therapy targeting the co-occurring driver mutations is a potential effective treatment for NSCLC patients. Further prospective study is still warranted to investigate the role of co-occurring driver mutations and the relevant treatment strategy.
摘要：
BRAF融合是非小细胞肺癌（NSCLC）中罕见的驱动癌基因。类似于BRAFV600E突变,它还可以激活MAPK信号通路。有一些病例报告表明对BRAF抑制剂的潜在反应及其作为从头驱动突变的重要作用。此外,同时发生的MET扩增已被定义为表皮生长因子受体(EGFR)突变型NSCLC患者的不良预后因素.目前,目前正在进行的临床试验研究MET扩增作为EGFR突变型NSCLC和奥希替尼获得性耐药患者的治疗靶点，这意味着MET扩增也具有治疗意义。然而,之前未在BRAF融合患者中对同时发生的MET扩增进行过研究.一名67岁的男子被诊断为转移性低分化腺癌。他接受了pembrolizumab和化疗联合的一线治疗，因为基因组检测显示野生型EGFR，免疫组织化学染色显示ALK和ROS1阴性。随着疾病进展，下一代测序显示KIAA1549-BRAF融合和MET扩增同时发生.随后的Dabrafenib,曲美替尼,卡马替尼联合治疗效果显著。针对共同发生的驱动突变的联合治疗是NSCLC患者的潜在有效治疗。仍需要进一步的前瞻性研究来研究共同发生的驱动突变的作用和相关的治疗策略。
