Human Oncology & Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, United States of America; Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro 88100, Italy.
Pharmacol Ther. 2019 Jul;199:188-196. doi: 10.1016/j.pharmthera.2019.03.010. Epub 2019 Apr 2.
HER2 activating mutations act as oncogenic drivers in various cancer types. In the clinic, they can be identified by next generation sequencing (NGS) in either tumor biopsies or circulating cell-free DNA (cfDNA). Preclinical data indicate that HER2 "hot spot" mutations are constitutively active, have transforming capacity in vitro and in vivo and show variable sensitivity to anti-HER2 based therapies. Recent clinical trials also revealed activity of HER2-targeted drugs against a variety of tumors harboring HER2 mutations. Here, we review the prevalence and type of HER2 mutations identified in different human cancers, their biochemical and biological characterization, and their sensitivity to anti HER2-based therapies in both preclinical and clinical settings.
HER2 激活突变在多种癌症类型中充当致癌驱动因子。在临床上，它们可以通过下一代测序（NGS）在肿瘤活检或循环无细胞 DNA（cfDNA）中检测到。临床前数据表明，HER2“热点”突变是组成性激活的，具有体外和体内转化能力，并对基于抗 HER2 的治疗具有不同的敏感性。最近的临床试验还揭示了针对多种携带 HER2 突变的肿瘤的 HER2 靶向药物的活性。在这里，我们回顾了不同人类癌症中鉴定的 HER2 突变的流行率和类型、它们的生化和生物学特征以及它们在临床前和临床环境中对基于抗 HER2 的治疗的敏感性。
