AACR 2026 Poster 2961

Developing Trastuzumab Deruxtecan-resistant Tumor Models for Efficacy Evaluation of Next-generation Anticancer Therapies

Jian Feng, Fuyin Zhao, Xinglong Dong, Aaron Li Hua, Chenpan Nie, Dorith Verstegen, Caitlyn Huisebosch, Wubin Qian, Sheng Guo, Jessie (Jingjing) Wang, Lenno Krenning, Marrit Putker, Ludovic Bourre, Peng Wang, Jun Zhou

Discover how ADC-resistant tumor models uncover mechanisms of resistance and enable next-generation therapy development.

Antibody-drug conjugates (ADCs) have transformed targeted cancer therapy, yet resistance remains a major barrier to sustained efficacy. This study demonstrates the development of ADC-resistant cell line, organoid, and in vivo models, providing a comprehensive platform to investigate resistance mechanisms and evaluate novel therapeutic strategies. By integrating functional assays with molecular analysis, these models support more predictive and translational ADC development.

Download this Poster to Discover:

• Understand key ADC resistance mechanisms: Explore the role of efflux transporters (ABCB1, ABCG2) and HER2 expression changes in driving resistance.
  
  
• Evaluate next-generation ADC performance: Assess responses to trastuzumab deruxtecan (Enhertu) and Dxd-based therapies across resistant models.
  
  
• Leverage clinically relevant organoid systems: Utilize CRISPR-engineered and drug-selected organoid models to study resistance and DNA damage responses.
  
  
• Validate findings in vivo: Confirm resistance phenotypes and therapeutic response using xenograft models.
  
  
• Support ADC optimization strategies: Inform payload selection, targeting approaches, and combination strategies to overcome resistance.

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