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.