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Editorial
. 2025 Jun 30;14(6):3286-3291.
doi: 10.21037/tcr-2025-400. Epub 2025 Jun 12.

Trastuzumab deruxtecan: expanding the role of HER2-targeted therapy in solid tumors

Hazem Aboaid  1 , Yin Mon Myat  2 , Daniel Thomas Jones  3 , Kyaw Zin Thein  4
Affiliations
Editorial

Trastuzumab deruxtecan: expanding the role of HER2-targeted therapy in solid tumors

Hazem Aboaid et al. Transl Cancer Res. .
No abstract available

Keywords: Trastuzumab deruxtecan (T-DXd); cell-free deoxyribonucleic acid (cfDNA); human epidermal growth factor receptor 2-targeted therapy (HER2-targeted therapy); immunohistochemistry (IHC); liquid biopsy.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-400/coif). K.Z.T. received honoraria from Targeted Oncology, MD Outlook, Curio Science, Aptitude Health, Inizio, OMNI-Oncology, and Onviv Expert Network; and served on the Advisory Board for EMD Serono and on the Speaker Bureau for Eisai, not related to this manuscript. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Trastuzumab deruxtecan mechanism of action. T-DXd is an antibody-drug conjugate composed of three key components: an anti-HER2 monoclonal antibody, a cleavable linker, and a cytotoxic payload. It targets cancer cells through antibody-dependent intracellular cytotoxicity, following a distinct sequence of events—1, T-DXd binds to the HER2 receptor on the surface of the cancer cell, blocking HER2 dimerization and disrupting its downstream signaling. 2, the drug is then delivered into the cancer cell via endocytosis. 3, an endolysosome is formed, facilitating the lysosomal degradation of T-DXd and releasing its cytotoxic payload. 4, the released cytotoxic payload translocates to the nucleus, where it directly disrupts DNA by inhibiting topoisomerase I. 5, this cascade of events ultimately results in cancer cell death. 6, T-DXd also exhibits a bystander effect, targeting neighboring cancer cells with little or no HER2 expression. Created in BioRender. Thein KZ. (2025) https://BioRender.com/x64z837. DNA, deoxyribonucleic acid; HER2, human epidermal growth factor receptor 2; T-DXd, trastuzumab deruxtecan.
See this image and copyright information in PMC

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References

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