Personalized treatment of HER2-positive lung adenocarcinoma using Human Organoid Drug Sensitivity Test

Human Epidermal Growth Factor Receptor 2 (HER2) mutations account for approximately 3% of non-small cell lung cancer (NSCLC) patients. Currently, targeted therapies for HER2-mutant NSCLC include HER2 tyrosine kinase inhibitors (TKIs) and HER2 Antibody-drug conjugates (ADC). However, resistance often develops, and effective treatments for HER2 mutations remain lacking. We report a case of HER2-mutant lung adenocarcinoma where the patient developed resistance and severe interstitial lung disease following antibody-drug conjugate therapy. A highly biomimetic Human Organoid (HO) platform was employed to screen potential therapeutic options for the patient. The HO results indicated efficacy of Sunvozertinib and ineffectiveness of ADC, with maximum half-maximal inhibitory concentration (IC50) values of 0.28 and 2.96, respectively. This case demonstrates the potential of Human Organoid Drug Sensitivity Test (HO-DST) to guide effective salvage therapy, bridging the gap between genomic profiling and functional drug response in precision oncology.人类表皮生长因子受体2（Human Epidermal Growth Factor Receptor 2, HER2）突变约占非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的3%。目前针对HER2突变型NSCLC的靶向治疗方案包括HER2酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs）与HER2抗体偶联药物（antibody-drug conjugates, ADC）。然而此类治疗常出现耐药现象，且目前仍缺乏针对HER2突变的有效治疗手段。本文报告1例HER2突变型肺腺癌患者，该患者在接受抗体偶联药物治疗后出现耐药及严重间质性肺病（interstitial lung disease）。研究采用高度仿生的人类类器官（human organoid, HO）平台为该患者筛选潜在治疗方案，类器官检测结果显示舒沃替尼（Sunvozertinib）具有抗肿瘤活性，而抗体偶联药物则无效，二者的半最大抑制浓度（half-maximal inhibitory concentration, IC50）分别为0.28与2.96。本案例证实了人类类器官药物敏感性检测（human organoid drug sensitivity test, HO-DST）在指导有效挽救治疗中的应用潜力，填补了精准肿瘤学（precision oncology）中基因组分型与功能药物反应之间的空白。