biostudies-literatureLuan TKey Research and Development Program of Shaoyang Science and Technology BureauStudy of the Carcinogenic Mechanisms and Molecular Characteristics in Primary Pulmonary Lymphoepithelioma-like CarcinomDevelopment and Industrialization of a Robotic Bronchoscopy PlatformMajor Project of Guangzhou National LaboratoryNational Natural Science Foundation of ChinaPlan on enhancing scientific research in GMU2629081https://www.ebi.ac.uk/biostudies/studies/S-EPMC12915762biostudies-literatureUnknown22(1)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 (IC<sub>5Human vaccines & immunotherapeuticsPersonalized treatment of HER2-positive lung adenocarcinoma using Human Organoid Drug Sensitivity Test.PMC129157622024B03J0862GMUCR2024-0101182570007GZNL2023A020112025B11110100012024GZ2023Yao LLuan YChen QFu SLuan TXie XMo JLin XLiu WWang LZhong NJin HChenli ZYu BWang SZhang YZhou CMa HMa KYang QXu YLv QfalsePersonalized 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 (IC<sub>52026-01-01T00:00:00Z2026 Dec2026-07-09T11:05:17.966Z2026-07-09T10:39:20.401ZS-EPMC129157624170089610.1080/21645515.2026.2629081