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Cancer therapy

Preventing HER2 degradation improves efficacy of trastuzumab deruxtecan

Nature Cancer (2026)Cite this article

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Methods to increase HER2 expression in breast cancer could expand the population eligible for treatment with trastuzumab deruxtecan (T-DXd), a HER2-directed antibody–drug conjugate. A study now reports that the membrane-bound E3 ligase FBXL2 regulates degradation of HER2, and FBXL2 inhibition sensitizes HER2-negative breast cancer cells to T-DXd.

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Fig. 1: Inhibition of FBXL2-mediated HER2 degradation enhances activity of trastuzumab deruxtecan.

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Authors and Affiliations

  1. Department of Discovery Oncology, Genentech, South San Francisco, CA, USA

    Gail D. Lewis

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  1. Gail D. Lewis
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Correspondence to Gail D. Lewis.

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The author is a full-time employee of Genentech and a shareholder of the Roche Group.

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Lewis, G.D. Preventing HER2 degradation improves efficacy of trastuzumab deruxtecan. Nat Cancer (2026). https://doi.org/10.1038/s43018-025-01106-x

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