Obermannová Radka, Lordick Florian
aClinic of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute and Faculty of Medicine, Masaryk University, Brno, Czech Republic bUniversity Cancer Center Leipzig (UCCL), University Hospital Leipzig, Leipzig, Germany.
Curr Opin Oncol. 2016 Jul;28(4):367-75. doi: 10.1097/CCO.0000000000000289.
The purpose of the review is to delineate novel approaches for biology-based treatment in advanced gastric cancer. We reviewed the latest translational and clinical research articles and congress presentations.
A new molecular classification of gastric cancer based on histology, genetic and proteomic alterations has evolved. It provides a roadmap for development of new drugs and combinations and for patient stratification. Anti-HER2 treatment, which is an effective strategy in metastatic gastric cancer, is now also being studied in the perioperative setting. However, resistance mechanisms in advanced disease are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is an emerging concept in the management of advanced gastric cancer, and ramucirumab has prolonged survival in the second line either as a monotherapy or in combination with paclitaxel. Biomarkers for selecting patients who benefit from ramucirumab are still lacking. Immune checkpoint blockade and inhibition of cancer stemness targets are other emerging directions for the medical treatment of gastric cancer. Large-scale international studies are ongoing.
Promising biology-based treatment strategies are evolving. But tumor heterogeneity which is an inherent feature of gastric cancer challenges the development of molecularly targeted and personalized treatment strategies.
本综述旨在阐述晚期胃癌基于生物学的新型治疗方法。我们回顾了最新的转化研究和临床研究文章以及大会报告。
基于组织学、基因和蛋白质组学改变的胃癌新分子分类已逐步形成。它为新药研发、联合用药及患者分层提供了路线图。抗HER2治疗在转移性胃癌中是一种有效策略，目前也正在围手术期进行研究。然而，晚期疾病中的耐药机制尚不清楚，最佳患者选择仍具有挑战性。靶向血管生成是晚期胃癌治疗中的一个新兴概念，雷莫西尤单抗作为单药或与紫杉醇联合使用均可延长二线治疗患者的生存期。目前仍缺乏用于选择能从雷莫西尤单抗治疗中获益患者的生物标志物。免疫检查点阻断和抑制癌症干性靶点是胃癌药物治疗的其他新兴方向。大规模国际研究正在进行中。
有前景的基于生物学的治疗策略正在不断发展。但肿瘤异质性作为胃癌的固有特征，对分子靶向和个性化治疗策略的发展构成了挑战。
