Department of Pathology, West China Hospital, Sichuan University, No.37, Guo Xue Xiang, Chengdu 610041, Sichuan, China.
Laboratory of Liver Transplantation, West China Hospital, Sichuan University, Chengdu 610041, China.
Life Sci. 2024 Nov 15;357:123087. doi: 10.1016/j.lfs.2024.123087. Epub 2024 Oct 2.
Being a member of the EGFR tyrosine kinase family, HER3 has been shown to be overexpressed in a number of cancers, including breast cancer (BC). The kinase activity of HER3 is extremely low, and it forms heterodimers with partners, HER2 in particular, that promote biological processes like cell migration, survival, and proliferation by activating downstream carcinogenic signaling pathways. The overexpression of HER3 is also directly linked to tumor invasion, metastasis, and a poor prognosis. Despite the relatively low expression of HER3 compared to EGFR and HER2, a lot of targeted drugs are making their way into clinical trials and seem to have a bright further. This review aims to summarize the relationship between HER3 overexpression, mutations, and carcinogenicity and drug resistance, starting from the unique structure and kinase activity of HER3. Simultaneously, numerous approaches to HER3 targeted therapy are enumerated, and the clinical detection methods for HER3 that are commonly employed in pathology are sorted and contrasted to offer physicians a range of options. We think that a better knowledge of the mechanisms underlying HER3 in tumors and the advancement of targeted HER3 therapy will contribute to an improved prognosis for cancer patients and an increase in the efficacy of anticancer therapies.
作为表皮生长因子受体(EGFR)酪氨酸激酶家族的一员,HER3 在多种癌症中过度表达,包括乳腺癌(BC)。HER3 的激酶活性极低,它与包括 HER2 在内的伴侣形成异二聚体,通过激活下游致癌信号通路,促进细胞迁移、存活和增殖等生物学过程。HER3 的过度表达也与肿瘤侵袭、转移和预后不良直接相关。尽管与 EGFR 和 HER2 相比,HER3 的表达相对较低,但许多靶向药物正在进入临床试验阶段,似乎有很好的前景。
本综述旨在从 HER3 的独特结构和激酶活性出发,总结 HER3 过表达、突变与致癌性和耐药性的关系。同时,列举了多种针对 HER3 的靶向治疗方法,并对病理科常用的 HER3 临床检测方法进行了分类和对比,为医生提供了多种选择。我们认为,更好地了解肿瘤中 HER3 的作用机制以及靶向 HER3 治疗的进展,将有助于改善癌症患者的预后并提高抗癌治疗的疗效。