Oscar Tahuahua, Medical Oncology Fellow at the National Cancer Institute of Mexico, shared a post on X about a paper by Monique Nilsson et al. published in Journal of Thoracic Oncology:
“Do HER2 mutant NSCLC tumors progressing on T DXd lose HER2 dependence?
No. Resistance is mainly driven by payload related mechanisms such as SLFN11 loss or ABCC1 gain, or impaired antibody binding due to domain IV mutations, rather than loss of the HER2 driver.
HER2 signaling persists, and tumors retain sensitivity to HER2 TKIs (zongertinib/poziotinib). Progression on TDXd opens a rational path to TKIs.”
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 Nilsson, Xiuning Le, Alissa Poteete, Xiaoxing Yu, Junqin He, Qian Huang, Yuji Shibata, Ximeng Liu, Cesar Moran, Ash 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 Weipert, Jing Wang, Ralf Kittler, John Heymach
Read the Full Article in Journal of Thoracic Oncology.
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