PDF(Pubmed)
Abstract：
Human epidermal growth factor receptor 3 (HER3), which is part of the HER family, is aberrantly expressed in various human cancers. Since HER3 only has weak tyrosine kinase activity, when HER3 ligand neuregulin 1 (NRG1) or neuregulin 2 (NRG2) appears, activated HER3 contributes to cancer development and drug resistance by forming heterodimers with other receptors, mainly including epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Inhibition of HER3 and its downstream signaling, including PI3K/AKT, MEK/MAPK, JAK/STAT, and Src kinase, is believed to be necessary to conquer drug resistance and improve treatment efficiency. Until now, despite multiple anti-HER3 antibodies undergoing preclinical and clinical studies, none of the HER3-targeted therapies are licensed for utilization in clinical cancer treatment because of their safety and efficacy. Therefore, the development of HER3-targeted drugs possessing safety, tolerability, and sensitivity is crucial for clinical cancer treatment. This review summarizes the progress of the mechanism of HER3 in drug resistance, the HER3-targeted therapies that are conducted in preclinical and clinical trials, and some emerging molecules that could be used as future designed drugs for HER3, aiming to provide insights for future research and development of anticancer drugs targeting HER3.
摘要：
人表皮生长因子受体3(HER3),是她家庭的一部分,在各种人类癌症中异常表达。由于HER3仅具有弱的酪氨酸激酶活性，当HER3配体神经调节素1（NRG1）或神经调节素2（NRG2）出现时，活化的HER3通过与其他受体形成异二聚体，有助于癌症发展和耐药性，主要包括表皮生长因子受体(EGFR)和人表皮生长因子受体2(HER2)。抑制HER3及其下游信号，包括PI3K/AKT,MEK/MAPK,JAK/STAT,和Src激酶，被认为是克服耐药性和提高治疗效率的必要条件。直到现在,尽管多种抗HER3抗体正在进行临床前和临床研究，由于HER3靶向疗法的安全性和有效性,因此均未获得用于临床癌症治疗的许可.因此,开发具有安全性的HER3靶向药物，耐受性,敏感性对临床癌症治疗至关重要。本文就HER3耐药机制的研究进展作一综述,在临床前和临床试验中进行的HER3靶向治疗，以及一些可用作HER3未来设计药物的新兴分子，旨在为未来针对HER3的抗癌药物的研发提供见解。
