Les options de traitement actuelles et émergentes pour les cancers gastro-œsophagiens HER2 positifs.
Résumé
Les cancers gastro-œsophagiens (incluant le cancer de l’œsophage, le cancer de la jonction gastro-œsophagienne et le cancer de l’estomac) représentent le cinquième type de cancer le plus fréquent et la deuxième cause de mortalité liée au cancer, avec 1,3 million de décès annuels dans le monde. L’incidence mondiale augmente, en particulier chez les jeunes patients. Les cancers gastro-œsophagiens (CGO) peuvent être classés en sous-types en fonction de la localisation anatomique, de l’histologie, des caractéristiques moléculaires ou de la biologie de la tumeur, et de la génomique. Une surexpression de HER2 est identifiée dans environ 20 % de tous les CGO. Le paysage des options thérapeutiques pour cette population de patients évolue rapidement. Cet article résume les progrès des thérapies ciblées contre le HER2 pour la maladie de stade avancé et met en lumière les orientations futures pour cibler la maladie.
La famille de récepteurs du facteur de croissance épidermique (EGFR) des récepteurs de la tyrosine kinase transmembranaire, EGFR/HER1, HER2/neu, HER3 et HER4, possèdent tous un domaine extracellulaire de liaison au ligand, un domaine transmembranaire lipophile et un domaine intracellulaire avec une activité tyrosine kinase. La liaison à ces récepteurs entraîne l’activation en aval des voies RAS/MAPK et PI3K/AKT. À son tour, cela induit la prolifération, la différenciation, la migration et la survie des cellules. L’essai de phase III (ToGA) sur le trastuzumab dans le cancer de l’estomac a révélé que l’incidence du cancer de l’estomac HER2 positif était de 22 %. Par conséquent, le fait de cibler le HER2 et ses voies de signalisation en aval présente un potentiel important en tant que stratégie thérapeutique. La Figure 1 illustre les mécanismes des cibles potentielles qui seront discutées dans cette revue.
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