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[胃癌的新型药物治疗方法]

[Novel pharmaceutical treatment approaches for gastric cancer].

作者信息

Lordick F

机构信息

Universitäres Krebszentrum Leipzig, Universitätsmedizin Leipzig, Liebigstr. 20, 04103, Leipzig, Deutschland.

出版信息

Pathologe. 2017 Mar;38(2):87-92. doi: 10.1007/s00292-017-0272-2.

Abstract

This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is a novel concept in the management of advanced gastric cancer. Ramucirumab is an antibody against vascular endothelial growth factor receptor 2 (VEGFR2) and prolongs survival in second-line treatment as a monotherapy and also in combination with paclitaxel; however, biomarkers for selection of patients who particularly benefit from antiangiogenic treatment are still lacking. Immune checkpoint blockade and inhibition of cancer stem cell targets are two emerging principles for the medicinal treatment of gastric cancer. Large-scale international studies for evaluation of these treatment approaches are ongoing. In summary, promising biology-based treatment strategies are evolving; however, tumor heterogeneity, which is an inherent feature of gastric cancer is a particular challenge for the development of targeted medications and a personalized treatment.

摘要

这篇综述文章阐述了胃癌药物治疗的新方法。基于组织学、遗传学、表观遗传学和蛋白质组学特征的胃癌新分子分类已逐步形成。它为新药及联合用药的研发以及临床研究中的患者分层提供了路线图,预计在不久的将来会被引入临床实践。抗HER2靶向治疗是转移性胃癌的一种有效治疗策略,目前也在围手术期进行研究,以提高接受根治性手术患者的缓解率并最终提高生存率;然而,HER2靶向治疗的耐药机制尚不清楚,最佳患者选择仍然具有挑战性。靶向血管生成是晚期胃癌治疗中的一个新概念。雷莫西尤单抗是一种抗血管内皮生长因子受体2(VEGFR2)抗体,作为单一疗法以及与紫杉醇联合使用时,均可延长二线治疗的生存期;然而,仍缺乏用于选择特别受益于抗血管生成治疗患者的生物标志物。免疫检查点阻断和癌症干细胞靶点抑制是胃癌药物治疗的两个新兴原则。评估这些治疗方法的大规模国际研究正在进行中。总之,基于生物学的有前景的治疗策略正在不断发展;然而,肿瘤异质性作为胃癌的一个固有特征,是靶向药物研发和个性化治疗的一个特殊挑战。

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