Fiche publication
Date publication
novembre 2025
Journal
Current oncology (Toronto, Ont.)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SCHOTT Roland
,
Dr BENDER Laura
Tous les auteurs :
Bischoff H, Gendarme S, Somme L, Chouaid C, Schott R
Lien Pubmed
Résumé
gene rearrangements define a distinct molecular subtype of non-small cell lung cancer (NSCLC), occurring in approximately 2% of cases and frequently associated with younger age, non-smoker status, and a high incidence of brain metastases. The discovery of ROS1 as an oncogenic driver has led to the development of targeted tyrosine kinase inhibitors (TKIs). Crizotinib first demonstrated substantial clinical benefit, but its limitations, including poor central nervous system (CNS) penetration and acquired resistance, highlighted the need for next-generation inhibitors. Several agents have since been developed, including entrectinib, lorlatinib, repotrectinib, taletrectinib, and zidesamtinib, each offering improved intracranial (IC) activity and efficacy against resistance mutations, notably . Despite these advances, optimal sequencing strategies remain undefined, and resistance ultimately emerges in most patients. This review provides an updated overview of ROS1 biology, diagnostic approaches, clinical outcomes with currently available TKIs, mechanisms of resistance, and ongoing challenges, emphasizing the rapidly evolving therapeutic landscape.
Mots clés
ROS1, brain metastases, non-small cell lung cancer, repotrectinib, resistance mutations, taletrectinib, targeted therapy, tyrosine kinase inhibitor, zidesamtinib
Référence
Curr Oncol. 2025 11 6;32(11):
