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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.

DOI:10.1007/s00292-017-0272-2
PMID:28220199
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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[Novel pharmaceutical treatment approaches for gastric cancer].[胃癌的新型药物治疗方法]
Pathologe. 2017 Mar;38(2):87-92. doi: 10.1007/s00292-017-0272-2.
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Targeting HER 2 and angiogenesis in gastric cancer.针对胃癌中的HER 2和血管生成
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Clinical impact of tumour biology in the management of gastroesophageal cancer.肿瘤生物学在食管癌管理中的临床影响
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引用本文的文献

1
[Gastric tumors].[胃肿瘤]
Pathologe. 2017 Mar;38(2):65-66. doi: 10.1007/s00292-017-0273-1.

本文引用的文献

1
Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial.帕博利珠单抗治疗 PD-L1 阳性晚期胃癌患者(KEYNOTE-012):一项多中心、开放标签、Ib 期临床试验。
Lancet Oncol. 2016 Jun;17(6):717-726. doi: 10.1016/S1470-2045(16)00175-3. Epub 2016 May 3.
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Clinical impact of tumour biology in the management of gastroesophageal cancer.肿瘤生物学在食管癌管理中的临床影响
Nat Rev Clin Oncol. 2016 Jun;13(6):348-60. doi: 10.1038/nrclinonc.2016.15. Epub 2016 Mar 1.
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Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction.
随机、双盲、安慰剂对照 III 期临床试验评价阿帕替尼用于化疗耐药的晚期或转移性胃或胃食管结合部腺癌患者的疗效。
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Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial.拉帕替尼联合卡培他滨和奥沙利铂治疗人表皮生长因子受体 2 阳性的晚期或转移性胃、食管或胃食管交界腺癌:TRIO-013/LOGiC——一项随机 III 期试验。
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A randomized Phase II trial of systemic chemotherapy with and without trastuzumab followed by surgery in HER2-positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301 (Trigger Study).一项针对HER2阳性伴广泛淋巴结转移的晚期胃癌或食管胃交界腺癌患者,对比单纯全身化疗与联合曲妥珠单抗全身化疗后行手术治疗的随机II期试验:日本临床肿瘤学会研究JCOG1301(触发研究)
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Randomized, Double-Blind Phase II Trial With Prospective Classification by ATM Protein Level to Evaluate the Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer.随机、双盲 II 期临床试验,前瞻性按 ATM 蛋白水平分类,以评估奥拉帕利联合紫杉醇治疗复发性或转移性胃癌患者的疗效和耐受性。
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Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes.胃癌的分子分析确定了与不同临床结果相关的亚型。
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The Lauren classification highlights the role of epithelial-to-mesenchymal transition in gastric carcinogenesis: an immunohistochemistry study of the STAT3 and adhesion molecules expression.劳伦分类法突出了上皮-间质转化在胃癌发生中的作用:一项关于信号转导和转录激活因子3(STAT3)及黏附分子表达的免疫组织化学研究
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