可克服曲妥珠单抗耐药性的HER2阳性胃癌新兴靶向治疗方法
Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance.
作者信息
Mitani Seiichiro, Kawakami Hisato
机构信息
Department of Medical Oncology, Faculty of Medicine, Kindai University, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan.
出版信息
Cancers (Basel). 2020 Feb 10;12(2):400. doi: 10.3390/cancers12020400.
Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody-drug conjugates that are under development and have shown promising antitumor activity in early studies.
曲妥珠单抗是一种针对人表皮生长因子受体2（HER2）的单克隆抗体，它提高了HER2阳性晚期胃癌或胃食管交界癌（AGC）患者的生存率。然而，对曲妥珠单抗不可避免地产生耐药性仍然是一个问题，在乳腺癌中已被证明有效的几种治疗策略在AGC中未能显示出临床益处。在这篇综述中，我们总结了对HER2靶向治疗耐药的潜在机制，并概述了在治疗对曲妥珠单抗难治的HER2阳性AGC方面过去和当前面临的挑战。我们还进一步描述了正在研发的新型药物，如HER2抗体药物偶联物，这些药物在早期研究中已显示出有前景的抗肿瘤活性。
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