Progress and challenges in HER2-positive gastroesophageal adenocarcinoma

Journal of Hematology & Oncology

Dan Zhao¹  Joseph Chao¹  Samuel J. Klempner² 

[1] 0000 0004 0421 8357, grid.410425.6, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Bldg. 51, 1500 E. Duarte Rd, 91010, Duarte, CA, USA;grid.488730.0, The Angeles Clinic and Research Institute, 90025, Los Angeles, CA, USA;0000 0001 2152 9905, grid.50956.3f, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 90048, Los Angeles, CA, USA;

关键词: Gastroesophageal cancer;    HER2;    Tumor heterogeneity;    Trastuzumab;    Next-generation sequencing;    Genomic profiling;    Circulating tumor DNA;   

DOI  :  10.1186/s13045-019-0737-2

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY