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

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, L...

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Bibliographic Details
Published in:NPJ precision oncology 2024-03, Vol.8 (1), p.29-29, Article 29
Main Authors: Villa, Matteo, Malighetti, Federica, Sala, Elisa, Sharma, Geeta G., Arosio, Giulia, Gemelli, Maria, Manfroni, Chiara, Fontana, Diletta, Cordani, Nicoletta, Meneveri, Raffaella, Zambon, Alfonso, Piazza, Rocco, Pagni, Fabio, Cortinovis, Diego, Mologni, Luca
Format: Article
Language:English
Subjects:
692/4028/67
692/4028/67/68
Biopsy
Brief Communication
Cancer Research
Cancer therapies
Chemotherapy
Cloning
Gene Therapy
Human Genetics
Inhibitor drugs
Internal Medicine
Kinases
Lung cancer
Medicine
Medicine & Public Health
Mutation
Oncology
Patients
Plasma
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Summary: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.
ISSN:2397-768X
2397-768X
DOI:10.1038/s41698-024-00498-w