Case Report: Heterogeneity of Resistance Mechanisms in Different Lesions Co-Mediate Acquired Resistance to First-Line Icotinib in EGFR Mutant Non-Small Cell Lung Cancer

Frontiers in Medicine

article

Zhicong Liu¹  Hui Dong¹  Wenyan Chen²  Bin Wang¹  Dongxiang Ji¹  Wei Zhang¹  Xuefei Shi¹  Xueren Feng¹ 

[1] Department of Respiratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University;Department of Respiratory Medicine, Huzhou Hospital, Zhejiang University School of Medicine

关键词: lung adenocarcinoma;    resistance mechanisms;    ALK rearrangement;    EGFR exon 20 T790M;    combination therapy;    case report;   

DOI  :  10.3389/fmed.2022.906364

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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, MET amplification, mesenchymal transformation, and anaplastic lymphoma kinase ( ALK ) 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 LCLAT1-ALK 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.

【 授权许可】

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