Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Bldg. 51, 1500 E. Duarte Rd, Duarte, CA, 91010, USA.
The Angeles Clinic and Research Institute, Los Angeles, CA, 90025, USA.
J Hematol Oncol. 2019 May 17;12(1):50. doi: 10.1186/s13045-019-0737-2.
HER2 expression remains an important biomarker to guide the addition of the monoclonal antibody trastuzumab to first-line systemic chemotherapy in unresectable, metastatic gastroesophageal adenocarcinomas (GEA). However, in contrast to breast cancer, other HER2-targeted strategies to date have not improved outcomes in this molecular subtype of GEA. Since the initial development of HER2 biomarker testing guidelines, significant spatial intratumoral heterogeneity of HER2 overexpression has been recognized as a major characteristic of this disease. In this review, we aim to survey the seminal positive and negative trials investigating HER2-targeted agents for GEA. We also highlight emerging data on the genomic and temporal heterogeneity of molecular resistance alterations that have yielded further insight into the heterogeneity of therapeutic responses. We conclude with an overview of promising novel agents and strategies which may refine the therapeutic landscape.
HER2 表达仍然是指导不可切除转移性胃食管腺癌（GEA）患者将单克隆抗体曲妥珠单抗加入一线全身化疗的重要生物标志物。然而，与乳腺癌不同，迄今为止，其他针对 HER2 的靶向策略并未改善这种 GEA 分子亚型的预后。自最初制定 HER2 生物标志物检测指南以来，HER2 过表达的显著空间肿瘤内异质性已被认为是该疾病的主要特征。在这篇综述中，我们旨在调查研究用于 GEA 的 HER2 靶向药物的主要阳性和阴性试验。我们还重点介绍了关于分子耐药性改变的时空异质性的新兴数据，这些数据进一步深入了解了治疗反应的异质性。最后，我们概述了有前途的新型药物和策略，这些药物和策略可能会改善治疗前景。
