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Review
. 2024 Nov;21(11):818-832.
doi: 10.1038/s41571-024-00939-2. Epub 2024 Sep 13.

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

Adrienne G Waks  1   2   3 , Olga Martínez-Sáez  4   5   6 , Paolo Tarantino  1   2   7 , Fara Braso-Maristany  4   5 , Tomás Pascual  4   5   6   8 , Javier Cortés  9   10   11 , Sara M Tolaney #  1   2   3 , Aleix Prat #  12   13   14   15   16
Affiliations
Review

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

Adrienne G Waks et al. Nat Rev Clin Oncol. 2024 Nov.

Abstract

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.

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