描绘HER2抑制剂耐药的生物标志物：对HER2阳性乳腺癌治疗的启示

Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.

作者信息

Cai Alvan, Chen Yuan, Wang Lily S, Cusick John K, Shi Yihui

机构信息

College of Medicine, California Northstate University, Elk Grove, CA 95757, USA.

Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany.

出版信息

Cancers (Basel). 2024 Jul 24;16(15):2635. doi: 10.3390/cancers16152635.

DOI:10.3390/cancers16152635

PMID:39123362

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11311605/

Abstract

HER2 (human epidermal growth factor receptor 2) is highly expressed in a variety of cancers, including breast, lung, gastric, and pancreatic cancers. Its amplification is linked to poor clinical outcomes. At the genetic level, HER2 is encoded by the ERBB2 gene (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), which is frequently mutated or amplified in cancers, thus spurring extensive research into HER2 modulation and inhibition as viable anti-cancer strategies. An impressive body of FDA-approved drugs, including anti-HER2 monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and HER2-tyrosine kinase inhibitors (TKIs), have demonstrated success in enhancing overall survival (OS) and disease progression-free survival (PFS). Yet, drug resistance remains a persistent challenge and raises the risks of metastatic potential and tumor relapse. Research into alternative therapeutic options for HER2+ breast cancer therefore proves critical for adapting to this ever-evolving landscape. This review highlights current HER2-targeted therapies, discusses predictive biomarkers for drug resistance, and introduces promising emergent therapies-especially combination therapies-that are aimed at overcoming drug resistance in the context of HER2+ breast cancer.

摘要

人表皮生长因子受体2（HER2）在多种癌症中高表达，包括乳腺癌、肺癌、胃癌和胰腺癌。其扩增与不良临床预后相关。在基因水平上，HER2由ERBB2基因（v-erb-b2禽成红细胞白血病病毒癌基因同源物2）编码，该基因在癌症中经常发生突变或扩增，因此促使人们对HER2调节和抑制作为可行的抗癌策略进行广泛研究。大量FDA批准的药物，包括抗HER2单克隆抗体（mAb）、抗体-药物偶联物（ADC）和HER2酪氨酸激酶抑制剂（TKI），已在提高总生存期（OS）和无疾病进展生存期（PFS）方面取得成功。然而，耐药性仍然是一个持续存在的挑战，并增加了转移潜能和肿瘤复发的风险。因此，研究HER2阳性乳腺癌的替代治疗方案对于适应这一不断变化的局面至关重要。本综述重点介绍了当前针对HER2的治疗方法，讨论了耐药性的预测生物标志物，并介绍了有前景的新兴治疗方法，特别是旨在克服HER2阳性乳腺癌背景下耐药性的联合治疗方法。