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

Tao Luan1,2,3,4, Suneng Fu1,4, Weiting Liu1,5

  • 1National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Human Vaccines & Immunotherapeutics
|February 17, 2026
PubMed

Insights

A case study highlights the challenge of resistance to antibody-drug conjugate therapy in Human Epidermal Growth Factor Receptor 2 (HER2)-mutant lung cancer. Human Organoid Drug Sensitivity Testing (HO-DST) identified Sunvozertinib as a promising salvage therapy option.

Area of Science:

  • Oncology
  • Genomics
  • Drug Discovery

Background:

  • Human Epidermal Growth Factor Receptor 2 (HER2) mutations occur in 3% of non-small cell lung cancer (NSCLC).
  • Current HER2-targeted therapies (TKIs, ADCs) face resistance, necessitating novel treatment strategies.
  • Interstitial lung disease is a severe complication of antibody-drug conjugate therapy.

Purpose of the Study:

  • To report a case of HER2-mutant lung adenocarcinoma with resistance to antibody-drug conjugate therapy.
  • To evaluate the utility of a Human Organoid (HO) platform for predicting therapeutic response.
  • To demonstrate the potential of Human Organoid Drug Sensitivity Test (HO-DST) in guiding salvage therapy.

Main Methods:

  • A patient with HER2-mutant lung adenocarcinoma resistant to ADC therapy was identified.
  • A biomimetic Human Organoid (HO) platform was utilized for drug screening.
  • Drug sensitivity was assessed using IC50 values derived from HO-DST.

Main Results:

  • The Human Organoid (HO) platform predicted Sunvozertinib efficacy (IC50=0.28) and ADC ineffectiveness (IC50=2.96).
  • This suggests Sunvozertinib as a potential salvage therapy for patients with acquired resistance.
  • HO-DST provided functional drug response data complementing genomic profiling.

Conclusions:

  • Human Organoid Drug Sensitivity Test (HO-DST) can guide effective salvage therapy selection in challenging NSCLC cases.
  • HO-DST bridges the gap between genomic data and clinical drug response.
  • This approach holds promise for advancing precision oncology in HER2-mutant NSCLC.
Keywords:
Drug Sensitivity Test (DST)Human Organoid (HO)biomimeticslung cancer

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