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Ref Type Journal Article
PMID (35503762)
Authors Koyama K, Ishikawa H, Abe M, Shiose Y, Ueno S, Qiu Y, Nakamaru K, Murakami M
Title Patritumab deruxtecan (HER3-DXd), a novel HER3 directed antibody drug conjugate, exhibits in vitro activity against breast cancer cells expressing HER3 mutations with and without HER2 overexpression.
Journal Vol Issue Date Pages Journal Short Title
PloS one 17 5 2022 e0267027 PLoS One
URL
Abstract Text ErbB3 (HER3), a member of the HER family, is overexpressed in various cancers and plays an important role in cell proliferation and survival. Certain HER3 mutations have also been identified as oncogenic drivers, making them potential therapeutic targets. In the current study, antitumor activity of patritumab deruxtecan (HER3-DXd), a HER3 directed antibody drug conjugate, was evaluated in tumor models with clinically reported HER3 mutations. MDA-MB-231, a HER3-negative human triple-negative breast cancer cell line, was transduced with lentiviral vectors encoding HER3 wild type (HER3WT), one of 11 HER3 mutations, or HER3 empty vector (HER3EV), in the presence/absence of HER2 overexpression. Targeted delivery of HER3-DXd was assessed using cell-surface binding, lysosomal trafficking, and cell-growth inhibition assays. HER3-DXd bound to the surface of HER3WT and mutant cells in a similar, concentration-dependent manner but not to HER3EV. HER3-DXd was translocated to the lysosome, where time- and concentration-dependent signals were observed in the HER3 mutant and HER3WT cells. HER3-DXd inhibited the growth of HER3WT and HER3 mutant cells. HER3-DXd activity was observed in the presence and absence of HER2 overexpression. These data suggest that HER3-DXd may have activity against tumors expressing wild type HER3 or clinically observed HER3 mutations, supporting further clinical evaluation.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
ERBB3 G325R missense unknown ERBB3 (HER3) G325R lies within the extracellular domain of the Erbb3 (Her3) protein (UniProt.org). G325R has been identified in the scientific literature (PMID: 35503762), but has not been biochemically characterized and therefore, its effect on Erbb3 (Her3) protein function is unknown (PubMed, Jan 2026).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB3 P262H breast cancer sensitive Patritumab deruxtecan Preclinical - Cell culture Actionable In a preclinical study, Patritumab deruxtecan (U3-1402) treatment inhibited growth of a breast cancer cell line expressing ERBB3 (HER3) P262H in culture (PMID: 35503762). 35503762
ERBB3 over exp breast cancer sensitive Patritumab deruxtecan Preclinical - Cell culture Actionable In a preclinical study, Patritumab deruxtecan (U3-1402) treatment inhibited growth of a breast cancer cell line overexpressing Erbb3 (Her3) in culture (PMID: 35503762). 35503762
ERBB3 A232V breast cancer sensitive Patritumab deruxtecan Preclinical - Cell culture Actionable In a preclinical study, Patritumab deruxtecan (U3-1402) treatment inhibited growth of a breast cancer cell line expressing ERBB3 (HER3) A232V in culture (PMID: 35503762). 35503762
ERBB3 G284R breast cancer sensitive Patritumab deruxtecan Preclinical - Cell culture Actionable In a preclinical study, Patritumab deruxtecan (U3-1402) treatment inhibited growth of a breast cancer cell line expressing ERBB3 (HER3) G284R in culture (PMID: 35503762). 35503762
ERBB3 E928G breast cancer sensitive Patritumab deruxtecan Preclinical - Cell culture Actionable In a preclinical study, Patritumab deruxtecan (U3-1402) treatment inhibited growth of a breast cancer cell line expressing ERBB3 (HER3) E928G in culture (PMID: 35503762). 35503762
ERBB3 D297Y breast cancer sensitive Patritumab deruxtecan Preclinical - Cell culture Actionable In a preclinical study, Patritumab deruxtecan (U3-1402) treatment inhibited growth of a breast cancer cell line expressing ERBB3 (HER3) D297Y in culture (PMID: 35503762). 35503762
ERBB3 T355I breast cancer sensitive Patritumab deruxtecan Preclinical - Cell culture Actionable In a preclinical study, Patritumab deruxtecan (U3-1402) treatment inhibited growth of a breast cancer cell line expressing ERBB3 (HER3) T355I in culture (PMID: 35503762). 35503762
ERBB3 V104L breast cancer sensitive Patritumab deruxtecan Preclinical - Cell culture Actionable In a preclinical study, Patritumab deruxtecan (U3-1402) treatment inhibited growth of a breast cancer cell line expressing ERBB3 (HER3) V104L in culture (PMID: 35503762). 35503762