Dual HER2 Inhibition: Mechanisms of Synergy, Patient Selection, and Resistance

Overview

Journal Nat Rev Clin Oncol

Specialty Oncology

Date 2024 Sep 13

PMID 39271787

Authors

Adrienne G Waks

Olga Martinez-Saez

Paolo Tarantino

Fara Braso-Maristany

Tomas Pascual

Javier Cortes

Sara M Tolaney

Aleix Prat

Affiliations

Soon will be listed here.

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.

Citing Articles

Investigation of Heterogeneity to Overcome Trastuzumab Resistance in HER2-Positive Breast Cancer.

Boz Er A Biology (Basel). 2025; 14(1).

PMID: 39857240 PMC: 11762810. DOI: 10.3390/biology14010009.

HER2DX genomic test in early-stage HER2-positive breast cancer.

Tolaney S, Tung N, Wolff A, DeMichele A, Cejalvo J, Martinez-Saez O ESMO Open. 2024; 9(12):103987.

PMID: 39710442 PMC: 11614791. DOI: 10.1016/j.esmoop.2024.103987.

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