Dual HER2 inhibition: mechanisms of synergy, patient selection, and resistance

Cet article passe en revue les mécanismes d'action des agents ciblant le récepteur HER2, examine les données scientifiques appuyant l'utilisation d'un double blocage de ce récepteur chez les patientes dont la tumeur mammaire présente une amplification du gène HER2 puis analyse le rôle des biomarqueurs dans l'orientation des futures stratégies thérapeutiques

Résumé en anglais

HER2-targeted therapies for patients with HER2+ breast cancer are rapidly evolving, offering a range of more complex and personalized treatment options. Currently, an array of anti-HER2 monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates are administered, sometimes alongside chemotherapy or endocrine therapy, both in curative and palliative contexts. However, the heterogeneous nature of HER2+ breast cancer demands a deeper understanding of disease biology and its role in responsiveness to novel HER2-targeted agents, as well as non-HER2-targeted therapies, in order to optimize patient outcomes. In this Review, we revisit the mechanisms of action of HER2-targeted agents, examine the evidence supporting the use of dual HER2 blockade in patients with HER2-amplified tumours, and explore the role of biomarkers in guiding future treatment strategies. We also discuss potential implications for the future treatment of patients with HER2+ breast cancer.