胃癌免疫治疗相关生物标志物的研究进展

胃癌作为一种常见的恶性肿瘤,具有较高的发病率和病死率,找到合适的治疗靶点和提高综合治疗效果迫在眉睫.既往胃癌的标准治疗手段以手术和化疗为主,但随着免疫治疗药物的不断完善以及有关程序性死亡受体1(PD-1)、程序性死亡受体配体1(PD-L1)等免疫检查点的临床试验不断开展,研究者发现免疫治疗能够有效辅助传统治疗,延长胃癌...     

结直肠癌免疫治疗生物标志物的研究进展

结直肠癌(CRC)是一种异质性疾病,治疗主要是以细胞毒性药物化疗为主.通过对其发病机制的研究发现存在很多表观遗传及遗传性因素.某些特异性生物标志物可以比肿瘤分期更好地预测临床表现及其预后.对患者进行常规分子检测有利于筛选出适合接受靶向药物及免疫治疗的患者.通过对KRAS、NRAS和BRAF突变的检测,DNA错配修复状态、肿瘤浸润淋巴细胞和检查点蛋白表达的分析有助于判断患者是否能从免疫治疗中获益.本文重点对CRC中一些相关的用于免疫治疗的生物标志物进行综述.     

肿瘤免疫治疗疗效和预后相关生物标志物的研究进展

[摘要] 免疫治疗是继传统的手术、化疗、放疗和靶向治疗后的一种新兴的肿瘤治疗手段。以免疫检查点抑制剂（ICP）疗法为代表的免疫治疗在肿瘤临床治疗中取得了突破性进展。随着ICP 在临床的应用,用于肿瘤诊断、疗效及预后的生物标志物的探索也成为肿瘤免疫治疗研究的热点。在当前精准医疗的背景下,多项临床研究证实程序性死亡蛋白配体-1（PD-L1）表达、肿瘤突变负荷、微卫星不稳定以及肿瘤微环境相关的生物标志物与免疫治疗的疗效密切相关。然而,许多患者并不能从这些疗法中受益,缺乏有效的疗效和预后生物标志物在很大程度上限制了其临床应用。本文总结了有关免疫治疗生物标志物的相关研究文献,重点关注免疫治疗疗效和预后生物标志物在临床应用的相关研究进展,阐述可能有助于指导临床决策及治疗方案选择的潜在生物标志物。     

血液学生物标志物在肺癌免疫治疗中的研究进展

生物标志物是一种可以客观衡量和评估机体生物学特征的指标,能反映抗肿瘤治疗的效果,指导临床用药策略的制定.目前,肺癌的治疗已进入以免疫检查点抑制剂(immune checkpoint inhibitor,ICI)为代表的免疫治疗时代,但并不是所有的患者都能从ICI治疗中获益,临床上用程序性死亡受体配体1、肿瘤突变负荷等生...     

PD-1/PD-L1免疫治疗在恶性肿瘤中的研究进展

<正>免疫治疗是肿瘤综合治疗的新热点,其中PD-1/PD-L1免疫治疗在很多恶性肿瘤治疗中发挥着重要作用,引起关注。目前,应用于临床治疗的靶向PD-1/PD-L1药物主要有Nivolumab、Pembromizumab和Atezolizumab等,在恶性肿瘤的治疗中已取得显著效果。     

PD-L2在血液系统肿瘤免疫治疗中的研究进展

随着程序性死亡受体1(programmed death receptor-1,PD-1)/程序性死亡受体配体1(programmed death-ligand 1,PD-L1)抑制剂在多种实体肿瘤临床治疗中取得广泛进展,血液系统肿瘤亦拉开了免疫疗法帷幕。然而,免疫检查点阻断疗法仍存在应答率低、药物耐药和副作用严重等挑战,需要进一步寻找新的免疫治疗靶点。B7家族中的程序性死亡受体配体2(programmed death-ligand 2,PD-L2)亦可以和PD-1结合,进而抑制免疫细胞功能。此外,PD-L2可以调控肿瘤免疫逃逸,在血液系统肿瘤中的治疗潜力仍有待研究。故本文对PD-L2的生物学特征、在血液系统肿瘤中的表达及在免疫治疗中的研究进展进行简要综述,为血液系统肿瘤通过PD-1/PD-L2通路治疗提供理论依据。     

基于PD-1/PD-L1 抑制剂的肺癌免疫治疗预测标志物的研究进展

[摘要] 近年来,免疫检查点抑制剂在肺癌治疗中取得突破性进展,正迅速改变着肺癌的治疗模式,也标志着免疫治疗2.0 时代的到来。新的肿瘤治疗模式对精准医学提出更高要求,对程序性死亡受体1（programmed death 1, PD-1）/程序性死亡配体1（programmed death ligand 1, PD-L1）抑制剂预后生物标志物也在不断地探索之中,主要包括以下几个方面：PD-L1 表达水平、肿瘤基因组异质性与肿瘤新抗原、T细胞特点、肿瘤微环境以及机体整体状态等。本文将针对目前PD-1/PD-L1 抑制剂在肺癌免疫治疗中的潜在生物标志物最新临床研究进展及其研究前景进行综述。     

PD-1/PD-L1介导的肿瘤免疫治疗的系统回顾及中医药联合的研究展望

肿瘤的免疫疗法在近年来取得了巨大的突破,肿瘤免疫微环境中的程序性死亡受体-1/程序性死亡配体-1(PD-1/PD-L1)通路是介导肿瘤免疫逃逸的重要途径,PD-1抑制剂的成功研发及初步临床运用揭示了其蕴含的巨大潜力.中医药是世界范围内治疗肿瘤的重要补充与替代医学手段之一,现有研究表明中医药可以改善机体免疫力,重塑肿瘤免...     

PD-1/PD-L1在肿瘤免疫逃逸中的作用机制及其临床应用

程序性死亡受体-1 (programmed death receptor-1,PD-1)是T细胞上主要存在的一种抑制性受体,与程序性死亡受体配体-1 (programmed death receptor ligand-1,PD-L1)相互作用,可抑制T细胞增殖、活化.在正常机体中,PD-1/PD-L1信号通路对维持机体的免疫耐受具有重要作用;而在肿瘤发生时,PD-1/PD-L1信号通路能抑制T细胞的免疫反应而促进肿瘤免疫逃逸的发生.本文从PD-1/PD-L1的发现及其结构、信号通路的作用机制、PD-1/PD-L1抗体在肿瘤免疫治疗中的应用等方面进行综述.     

免疫治疗相关心脏不良事件实体瘤2例及文献复习

恶性肿瘤严重威胁着人类的生命与健康,发病率逐年增高,也是目前引起死亡的最主要原因之一 [1].恶性实体瘤的治疗选择有限,预后欠佳.随着免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)在多种实体瘤中表现出优越的抗肿瘤活性,这一新兴的治疗方式在世界范围内得到快速推广.然而,ICIs治疗...     

Pharmacogenetics in gastrointestinal tumors

Treatment of gastrointestinal cancers has significantly advanced over the last few years with the introduction of effective chemotherapeutic and targeted drugs. To provide individual treatment with low toxicity on the one hand but maximum benefit on the other hand is still an unsolved problem. Interindividual variation of drug toxicity and efficacy is determined by genetic polymorphisms. The genetic approach based on single-gene (pharmacogenetics) or multi-gene (pharmacogenomics) analyses is developing as a valuable tool to design tailored therapy. This review focuses on clinically significant polymorphisms in genes involved in the metabolism of the major players in the chemotherapy of gastrointestinal cancer: fluoropyrimidines, irinotecan and platinum. In addition, first results of pharmacogenetics in targeted therapy including cetuximab and bevacizumab are discussed. The pharmacogenetic approach to individualize therapy in gastrointestinal cancers is promising, but additional larger and controlled studies are needed to justify changes of treatment strategies.     

胃肠间质瘤的外科治疗问题

 靶向治疗的问世使得胃肠间质瘤（GIST）的治疗发生了革命性的变化，但依然应强调外科原则和技巧在治疗GIST中的重要性。对位于食管、胃肠道、结直肠的GIST病例的治疗经验进行了总结。术中外科医师应尽可能完整切除肿瘤，如果术中无法完整切除，可予伊马替尼治疗。由于GIST甚少经淋巴途径转移，故不必常规行淋巴结清扫术。     

Mouse models of gastrointestinal tumors

The laboratory mouse (Mus musculus) has become one of the best model animal species in biomedical research today because of its abundant genetic/genomic information, and easy mutagenesis using transgenic and gene knockout technology. Genetically engineered mice have become essential tools in both mechanistic studies and drug development. In this article I will review recent topics in gastrointestinal cancer model mice, with emphasis on the results obtained in our laboratory. They include: (i) mouse models for familial adenomatous polyposis (Apc mutant mice; modifier genes of Apc intestinal polyposis; stabilizing beta-catenin mutant mice); (ii) mouse models for colon cancer (mouse models for hereditary non-polyposis colon cancer; additional mutations in Apc mutant mice; models with mutations in other genes; models for colon cancer associated with inflammatory bowel diseases); and (iii) mouse models for gastric cancer.     

Special considerations in pediatric gastrointestinal tumors

Pediatric gastrointestinal tumors are rare in children but are being increasingly recognized. These tumors have distinct biologic and clinical feature that are different from those observed in adults. This review highlights the biological and clinical characteristics of pediatric GIST and provides diagnostic and therapeutic guidelines for the management these unique and challenging group of tumors.     

Imatinib resistance in gastrointestinal stromal tumors

Conventional chemotherapeutic drugs are ineffective in treatment of gastrointestinal stromal tumors (GISTs). Imatinib (STI571, Gleevec, Glivec; Novartis Pharmaceuticals, East Hanover, NJ), a selective inhibitor of KIT, ABL, BCR-ABL, PDGFRA, and PDGFRB, represents a new paradigm of targeted cancer therapy and has revolutionized the treatment of patients with chronic myelogenous leukemia and GISTs. Unfortunately, imatinib resistance has emerged. The reported mechanism of imatinib resistance in GISTs involves missense mutation in the kinase domain of KIT, including Thr670Ile, Tyr823Asp, and Val654Ala. The established mechanisms and potential mechanisms of imatinib resistance in GISTs, the imaging studies indicative of early development of imatinib resistance, and the management of imatinib-resistant GISTs are discussed.     

蛋白质组学在消化系肿瘤标记物检测中的应用

利用蛋白质组学方法进行肿瘤标记物筛选是当前疾病研究中的一个热点,蛋白质组学为消化系肿瘤标记物的研究提供了重要工具,一些特异性标记物相继被发现.现综述蛋白质组学在消化系肿瘤标记物研究中的应用.     

MicroRNAs as potential biomarkers in human solid tumors

MicroRNAs (miRNAs) regulate the expression of approximately 30% of protein-coding genes. Functions of miRNAs are essential to maintain a steady state of cellular machinery. Dysregulations of miRNAs play pivotal roles in the initiation and progression of malignancies. Abnormal miRNA expressions have been found in a variety of human solid tumors. Furthermore, extracellular miRNAs could circulate in body fluids, and hence show great promise for refining diagnosis and prognosis of cancer. Here we review the progress of analysis of microRNAs as a potential approach for diagnosis and prognosis of solid cancer. We will also discuss obstacles in developing miRNAs as circulating biomarkers.