New pan-ALK inhibitor-resistant EML4::ALK mutations detected by liquid biopsy in lung cancer patients

作者：M. Villa, F. Malighetti, Elisa Sala, G. Sharma, Giulia Arosio, M. Gemelli, Chiara Manfroni, D. Fontana, N. Cordani, Raffaella Meneveri, Alfonso Zambon, R. Piazza, F. Pagni, D. Cortinovis, L. Mologni · 发表于：npj Precision Oncology · 年份：2024 · DOI：10.1038/s41698-024-00498-w · 被引用次数：8 · 研究领域：Medicine

ALK and ROS1 fusions are effectively targeted by tyrosine kinase inhibitors (TKIs), however patients inevitably relapse after an initial response, often due to kinase domain mutations. We investigated circulating DNA from TKI-relapsed NSCLC patients by deep-sequencing. New EML4::ALK substitutions, L1198R, C1237Y and L1196P, were identified in the plasma of NSCLC ALK patients and characterized in a Ba/F3 cell model. Variants C1237Y and L1196P demonstrated pan-inhibitor resistance across 5 clinical and 2 investigational TKIs.