Sappenfield Ryan, Mehlhaff Eric, Miller Devon, Ebben Johnathan E, Uboha Nataliya V
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, 53792, USA.
Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA.
J Gastrointest Cancer. 2024 Jun;55(2):549-558. doi: 10.1007/s12029-023-01007-1. Epub 2024 Jan 27.
Biomarker-based therapies have shown improved patient outcomes across various cancer types. The purpose of this review to summarize our knowledge of current and future biomarkers in esophagogastric adenocarcinoma (EGA).
In this publication, we will review current standard biomarkers in patients with upper GI cancers. We will also discuss novel biomarkers that are under investigations and their associated therapies that are currently in clinical trials.
EGAa are a group of heterogeneous diseases, both anatomically and molecularly. There are several established biomarkers (HER2, PD-L1, microsattelite instability or mismatch repair protein expression) that allow for individualized treatments for patients with these cancers. There are also several emerging biomarkers for EGA, some of which have clinically relevant associated therapies. Claudin 18.2 is the furthest along among these. Anti-claudin antibody, zolbetuximab, improved overall survival in biomarker select patients with advanced GEA in two phase 3 studies. Other novel biomarkers, such as FGFR2b and DKN01, are also in the process of validation, and treatments based on the presence of these biomarkers are currently in clinical studies.
Ongoing efforts to identify novel biomarkers in EGA have led to enhanced subclassification of upper GI cancers. These advances, coupled with the strategic application of targeted therapies and immunotherapy when appropriate, hold promise to further improve patients outcomes.
基于生物标志物的疗法已在多种癌症类型中显示出改善患者预后的效果。本综述的目的是总结我们对食管胃腺癌(EGA)当前和未来生物标志物的认识。
在本出版物中,我们将回顾上消化道癌症患者的当前标准生物标志物。我们还将讨论正在研究的新型生物标志物及其目前正在进行临床试验的相关疗法。
EGA在解剖学和分子水平上都是一组异质性疾病。有几种已确立的生物标志物(HER2、PD-L1、微卫星不稳定性或错配修复蛋白表达)可用于为这些癌症患者提供个体化治疗。EGA也有几种新兴的生物标志物,其中一些具有临床相关的联合疗法。Claudin 18.2在这些生物标志物中进展最为显著。在两项3期研究中,抗Claudin抗体zolbetuximab改善了生物标志物选择的晚期GEA患者的总生存期。其他新型生物标志物,如FGFR2b和DKN01,也在验证过程中,基于这些生物标志物存在情况的治疗目前正在进行临床研究。
在EGA中识别新型生物标志物的持续努力导致了上消化道癌症的进一步细分。这些进展,再加上在适当的时候有针对性地应用靶向治疗和免疫治疗,有望进一步改善患者的预后。