: 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.
New pan-ALK inhibitor-resistant EML4::ALK mutations detected by liquid biopsy in lung cancer patients / 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. - In: NPJ PRECISION ONCOLOGY. - ISSN 2397-768X. - 8:1(2024), pp. 1-8. [10.1038/s41698-024-00498-w]
New pan-ALK inhibitor-resistant EML4::ALK mutations detected by liquid biopsy in lung cancer patients
Sala, Elisa;Zambon, Alfonso;
2024
Abstract
: 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.
| File | Dimensione | Formato | |
|---|---|---|---|
|
s41698-024-00498-w (1).pdf
Open access
Tipologia:
Versione pubblicata dall'editore
Dimensione
2.81 MB
Formato
Adobe PDF
|
2.81 MB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris
