人表皮生长因子受体3（HER3）是人类表皮生长因子受体家族的成员，其主要配体为神经调节素1和2。虽然其酪氨酸激酶活性较差，自身的致癌能力较弱，但HER3可以与HER2和/或表皮生长因子受体（EGFR）异二聚化，从而极大增强跨磷酸化并激活下游信号转导途径，最终促进肿瘤发生、转移和药物抗性。考虑到其在实体肿瘤中的广泛表达，已经进行了多项努力，通过阻断其配体结合域或与其他受体二聚化来治疗靶向HER3。然而，使用抗-HER3单克隆抗体或双特异性抗体，无论是单用还是与其他化合物联合使用，都不幸在几种肿瘤类型中产生不令人满意的结果。最近，通过抗体-药物偶联物将细胞毒素有效送达到HER3上已在几种肿瘤中展现出有希望的活性，这表明在癌症治疗中，靶向HER3具有潜在的作用。Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Human epidermal growth factor receptor 3 (HER3) is a member of the human epidermal growth factor receptors family, having as its main ligands neuregulins 1 and 2. Although its poor tyrosine kinase activity entails a weak oncogenic power on its own, HER3 can heterodimerize with HER2 and/or epidermal growth factor receptor (EGFR), leading to a drastic enhancement of transphosphorylation and activation of downstream signaling pathways, ultimately promoting oncogenesis, metastatic dissemination, and drug resistance. Given its ubiquitous expression across solid tumors, multiple efforts have been done to therapeutically target HER3 by blocking either the ligand binding domain or its dimerization with other receptors. Treatment with anti-HER3 monoclonal antibodies or bispecific antibodies, both as single agents and in combination with other compounds, unfortunately led to unsatisfactory results across several tumor types. The HER3-directed delivery of cytotoxic payloads through antibody-drug conjugates has recently demonstrated encouraging activity in several tumor types, however, suggesting a potential role for the therapeutic targeting of HER3 in cancer treatment.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.