Les inhibiteurs de KRAS dans le cancer du poumon : stratégies actuelles et approches futures
Résumé
Les protéines RAS (homologue de l’oncogène viral du sarcome du rat) ont été parmi les premières protéines qui régulent la croissance, la différenciation et la survie des cellules à être identifiées. Les travaux précurseurs de Harvey et Kirsten dans les années 1960 ont ouvert la voie à la découverte de ces protéines codées par des oncogènes rétroviraux d’abord observés dans les virus du sarcome de rat. Parmi les différentes protéines RAS découvertes à ce jour, l’isoforme KRAS (homologue de l’oncogène viral du sarcome du rat de Kirsten) est la plus fréquemment mutée dans les cancers humains, apparaissant dans 75 à 80 % des cancers, suivie par le RAS du neuroblastome (NRAS), apparaissant dans 12 %, et le RAS de Harvey (HRAS), apparaissant dans 3 % des cancers RAS. Le KRAS, le récepteur de facteur de croissance épidermique (EGFR) ainsi que la kinase du lymphome anaplasique (ALK), sont les oncoprotéines les plus couramment identifiées avec des mutations connues dans le cancer du poumon non à petites cellules (CPNPC), et ont fait l’objet de nombreuses études au fil des ans. Malgré des succès significatifs à cibler les mutations de EGFR et de ALK dans le CPNPC, des progrès restent à faire dans le développement de thérapies pour les mutations de KRAS.
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