Department of Medical Oncology, Institut Català d'Oncologia (ICO) Badalona, 08916 Badalona, Spain.
Badalona Applied Research Group in Oncology (B-ARGO), 08916 Badalona, Spain.
Int J Mol Sci. 2023 Jul 13;24(14):11403. doi: 10.3390/ijms241411403.
Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10-20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, this being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody-drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.
胃癌是一种侵袭性疾病，近年来全球发病率呈上升趋势。约有 10-20%的胃癌过度表达人表皮生长因子受体 2（HER2）。针对 HER2 的靶向治疗作为转移性疾病标准治疗的一部分的实施，改善了这部分患者的预后。然而，胃癌的死亡率仍然很高，迫切需要新的治疗策略。免疫疗法与 HER2 靶向治疗的联合在临床前模型中显示出协同作用，这是在局部晚期和转移性环境中探索这种联合的理论基础。此外，抗体药物偶联物和其他新型 HER2 靶向药物的出现，导致了大量临床试验的开展，并取得了有前景的结果。这篇综述介绍了支持 HER2 靶向药物与免疫疗法联合使用的分子机制，并概述了 HER2 阳性疾病的治疗现状。我们关注免疫疗法的作用，但也总结了正在进行的临床研究中的新兴疗法和联合治疗，这些可能会改变未来 HER2 阳性疾病的标准治疗。
