Liu Zhicong, Dong Hui, Chen Wenyan, Wang Bin, Ji Dongxiang, Zhang Wei, Shi Xuefei, Feng Xueren
Department of Respiratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China.
Department of Respiratory Medicine, Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China.
Front Med (Lausanne). 2022 Jul 7;9:906364. doi: 10.3389/fmed.2022.906364. eCollection 2022.
Epidermal growth factor receptor (EGFR)-activating mutations are major oncogenic mechanisms in non-small cell lung cancer (NSCLC). Most patients with NSCLC with EGFR mutations benefit from targeted therapy with EGFR- tyrosine kinase inhibitors (TKIs). One of the main limitations of targeted therapy is that the tumor response is not durable, with the inevitable development of drug resistance. Previous studies demonstrated that the potential resistance mechanisms are diverse, including the presence of EGFR T790M, amplification, mesenchymal transformation, and anaplastic lymphoma kinase () rearrangement. The patient in our report was diagnosed with stage IA lung adenocarcinoma harboring the EGFR L858R mutation and underwent radical surgery. The patient received icotinib for 12 months after recurrence. Subsequent molecular analysis of the left pleural effusion indicated that fusion might be an underlying mechanism contributing to the acquired resistance to icotinib. Ensartinib was prescribed, but the lesion in the right lung continued to progress. Hence, a re-biopsy and molecular analysis of lesions in the right lung was performed to solve this problem. In contrast to the left pleural effusion, EGFR exon 20 T790M might have mediated the acquired resistance in lesions in the right lung of this patient. The combination of osimertinib and ensartinib has achieved a rapid partial response until now. The complexity and heterogeneity in our case may provide new insights into the resistance mechanisms of targeted therapy.
表皮生长因子受体(EGFR)激活突变是非小细胞肺癌(NSCLC)的主要致癌机制。大多数具有EGFR突变的NSCLC患者受益于EGFR酪氨酸激酶抑制剂(TKIs)的靶向治疗。靶向治疗的主要局限性之一是肿瘤反应不持久,不可避免地会产生耐药性。先前的研究表明,潜在的耐药机制多种多样,包括EGFR T790M的存在、扩增、间质转化和间变性淋巴瘤激酶(ALK)重排。我们报告中的患者被诊断为患有EGFR L858R突变的IA期肺腺癌,并接受了根治性手术。患者复发后接受了12个月的埃克替尼治疗。随后对左侧胸腔积液进行的分子分析表明,ALK融合可能是导致对埃克替尼获得性耐药的潜在机制。给予了恩沙替尼,但右肺病变持续进展。因此,对右肺病变进行了再次活检和分子分析以解决这个问题。与左侧胸腔积液不同,EGFR外显子20 T790M可能介导了该患者右肺病变的获得性耐药。奥希替尼和恩沙替尼的联合应用至今已取得快速部分缓解。我们病例中的复杂性和异质性可能为靶向治疗的耐药机制提供新的见解。