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.
人表皮生长因子受体2（HER2）在多种癌症中高度表达，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。在基因层面，HER2由ERBB2基因（v-erb-b2禽类成红细胞白血病病毒癌基因同源物2）编码，该基因在癌症中常发生突变或扩增，从而推动了对HER2调控与抑制作为有效抗癌策略的广泛研究。美国食品药品监督管理局已批准多类药物，包括抗HER2单克隆抗体、抗体偶联药物以及HER2酪氨酸激酶抑制剂，这些药物在提高患者总生存期和无进展生存期方面成效显著。然而，耐药性问题仍是持续存在的挑战，并增加了肿瘤转移和复发的风险。因此，针对HER2阳性乳腺癌的替代治疗方案研究，对于适应这一不断演变的治疗格局至关重要。本综述重点阐述了当前HER2靶向治疗策略，探讨了预测耐药性的生物标志物，并介绍了有望克服HER2阳性乳腺癌耐药性的新兴疗法，尤其是联合治疗方案。
肿瘤(癌症)患者之家