Xiuning Le, Associate Professor, Deputy Section Chief of Thoracic Medical Oncology at MD Anderson Cancer Center, shared a post on LinkedIn about a recent article by Monique B. Nilsson et al, published in Journal of Thoracic Oncology:
“New online from our group at mdanderson International Association for the Study of Lung Cancer Mechanisms of Resistance to Trastuzumab-DXd in Lung Cancer
Key findings:
- Payload resistance driven by SLFN11 loss and copy-number gains in the efflux pump ABCC1/MRP1
- Secondary HER2 extracellular domain mutations at the antibody binding site (e.g., D582, F595)
- Tumors with acquired payload resistance or domain IV mutations retain HER2 signaling and remain sensitive to HER2 TKIs, including zongertinib and sevabertinib
This is the first comprehensive preclinical and clinical investigation of ADC mechanisms of resistance in lung cancer, with direct therapeutic implications.”
Title: Loss of payload sensitivity and other mechanisms of resistance to T-DXd in HER2-mutant NSCLC: implications for subsequent responsiveness to HER2 TKIs
Authors: Monique B. Nilsson, Xiuning Le, Alissa Poteete, Xiaoxing Yu, Junqin He, Qian Huang, Yuji Shibata, Ximeng Liu, Cesar Moran, Ash A. Alizadeh, Maximilian Diehn, Heather Wakelee, Diego Almanza, Scott Soltys, Takeshi Sugio, Jurik Mutter, Xiaoman Kang, Rui Wang, Soyeong Jun, Mohammad Shahrokh Esfahani, Hai Tran, Yuanxin Xi, Lingzhi Hong, Xiaofang Huo, Ashwani Kumar, Xiaoyang Ren, Kei Oguchi, Kazuhisa Minamiguchi, Caroline M. Weipert, Jing Wang, Ralf Kittler, John V. Heymach
Read the Full Article on Journal of Thoracic Oncology
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