晚期肺鳞癌靶向及免疫治疗进展

肺癌是目前世界上发病率和死亡率最高的恶性肿瘤。其中,肺鳞癌（squamous-cell lung cancer,SQCLC）为一种常见的病理类型。近年来,许多学者针对肺鳞癌的靶向药物与免疫制剂进行大量的科学研究及临床试验,EGFR单克隆抗体、VEGFR的单克隆抗体、免疫检查点抑制剂等多种药物已在临床试验中取得了一定成果。本文对晚期肺鳞癌的分子靶向治疗及免疫治疗进行系统性的阐述,通过分析其在提高患者生存率、改善生存质量等方面取得的实质性研究成果,探讨目前临床上晚期肺鳞癌的靶向及免疫治疗进展及未来发展方向。     

血液肿瘤靶向治疗和免疫治疗

 引言恶性肿瘤治疗的目的仍然是在不损伤正常组织的前提下 ,长时期根治肿瘤。近年来 ,血液肿瘤治疗的最大进步在于靶向和免疫治疗的基础研究和临床应用。1　靶向治疗肿瘤靶向治疗包括单克隆抗体 (单抗 )、基因和酶抑制等的靶向治疗。借助高度特异的亲肿瘤细胞物质为载体 (如单抗 ) ,发挥特异性导向功能 ,通过抗体依赖细胞介导的细胞毒作用 (ADCC) ,或利用单抗与具有细胞毒作用的物质 (放射性核素、化学药物或毒素等 )结合 ,将细胞毒物质尽量集中在肿瘤细胞部位发挥杀伤作用 ;而基因和酶抑制的靶向治疗则是通过特异性封闭了目的基因的表达或抑制酶的活性而达到抑制肿瘤增殖的目的。1.1　单克隆抗体目前所研制的抗肿瘤靶向药物还是以单抗为主 ,1997年第一个治疗性单抗 (抗CD2 0单抗 ,美罗华 ,Rituximab)问世 ,美罗华对CD2 0 +低度恶性B细胞恶性淋巴瘤治疗效果令人振奋 ,对常规化疗后复发的低度恶性或滤泡型恶性淋巴瘤也有良好效果。使人们对单抗的靶向治疗效果寄予希望。针对CD33+AML细胞的HuM 195 (人源化CD33单抗 )则是另一个比较成功的治疗性单抗。但单独应用单抗的效果仍不理想 ,通过单抗与...     

癌症免疫治疗和靶向治疗的相互作用

最近,对癌症发病机制的深入了解已经促进了新的治疗方法,如靶向药物治疗和癌症免疫治疗。靶向治疗旨在抑制维持肿瘤生长的至关重要的分子通路;而免疫治疗是刺激宿主的免疫反应,以达到长期的肿瘤抑制。靶向治疗也可以调节免疫系统,因此提出一种可能性,联合靶向治疗和免疫治疗可能有效地改善临床结果。     

宫颈癌靶向治疗和免疫治疗研究进展

宫颈癌患者病死率位居女性恶性肿瘤前列,严重威胁女性的生命健康。近年来,得益于靶向治疗和免疫治疗研究的发展,尤其是抗血管生成药物贝伐单抗的使用,宫颈癌患者的生存时间得到了显著延长,然而仍有部分患者疗效不佳。肿瘤分子分型从分子层面对宫颈癌进行亚型划分,可进一步区分靶向治疗及免疫治疗适应人群,有望提升临床治疗效果。现针对宫颈癌靶向治疗及免疫治疗的基础研究、临床试验及其分子分型最新进展进行系统综述。     

胃癌靶向治疗与免疫治疗的新进展

近几年,癌症基因组图谱计划的研究者们依据胃癌患者不同的临床与分子生物学特点将胃癌分为四种不同的亚型,以此来指导靶向药物的临床试验和应用。该分型的主要目的在于靶向药物的个体化治疗。有两种靶向药物,分别为曲妥珠单抗和雷莫卢单抗,已被批准用于晚期胃癌患者的治疗。而且,胃癌免疫治疗也取得了许多进展。虽然晚期胃癌的许多免疫治疗药物尚处于临床研究阶段,但是免疫治疗仍是一个充满应用前景的治疗手段。本文主要对胃癌领域靶向治疗与免疫治疗的最新研究进展做一系统综述。     

转移性肾癌靶向治疗和免疫治疗的现状与进展

近年来,转移性肾癌的治疗方式从细胞因子药物的治疗,到现在的针对血管生成、哺乳动物的雷帕霉素途径、免疫应答的药物的应用发生了巨大的变化。尽管耐药仍然是一个巨大的挑战,但通过对这些药物的应用及药物联合应用,转移性肾癌的治疗疗效得到大大的提高。目前新的治疗方法正在迅速发展,治疗前景一片大好。     

难治性甲状腺癌靶向治疗Meta分析

目的 目前对于进展期甲状腺癌分子靶向治疗的研究多为单臂实验,RCT研究较少.本研究应用Meta分析方法,评价分子靶向治疗在难治性甲状腺癌中的疗效和安全性,以期为其应用提供理论基础.方法 检索纳入1989-01-2015-01 Medline、Web of science、Cochrane Central、EBSCO、Embase等英文数据库及中国学术期刊全文数据库、万方、维普等中文数据库中的文献.按照纳入与排除标准进行文献筛选和质量评价后,利用Cochrane中心提供的RevMan5.0软件对数据进行分析.主要评价指标是患者的无进展生存率及药物的不良反应.结果 共纳入4项随机对照试验研究,得到药物组总体样本730例,对照组(安慰剂组)总体样本493例.相比对照组,药物组6、12和18个月的无进展生存率均显著提高(6个月:RR=2.57,95％CI为1.97～3.35;12个月:RR=2.01,95％CI为1.53～2.65;18个月:RR=2.10,95％CI为1.54～2.87).药物组不良反应发生率高于对照组(RR=4.20,95％CI为2.82～6.24).主要是腹泻、疲劳、高血压、手足综合征和QT间期延长.结论 靶向药物可显著延长难治性甲状腺癌患者的无进展生存期.虽然其不良反应发生率显著高于对照组,但患者仍可耐受.靶向治疗为难治性甲状腺癌患者带来新的希望.     

靶向免疫治疗联合放射治疗在晚期黑色素瘤中的研究进展

黑色素瘤是皮肤癌中最具侵袭性、死亡率较高的恶性肿瘤。Ⅰ、Ⅱ期黑色素瘤采取手术切除可完全治愈,Ⅲ、Ⅳ期黑色素瘤应用传统的手术、放化疗方案治疗效果不理想,预后差。近年来,随着对Ⅲ、Ⅳ期黑色素瘤治疗方案的探索,靶向免疫治疗取得了显著疗效。靶向免疫药物可抑制负性调节因子,增强全身抗肿瘤免疫效应。放疗在杀死局部肿瘤的同时,也可增强全身免疫应答。近期研究发现,靶向免疫联合放射治疗可增强对肿瘤局部和远处的控制作用,延长患者总体生存期,两者联合治疗优于单一治疗方案。本文对上述研究领域内的进展进行综述。      

甲状腺癌免疫治疗的研究进展

摘 要：甲状腺癌是内分泌系统中最常见的恶性肿瘤,其组织学类型主要有乳头状癌(PTC)、滤泡状癌(FTC)、髓样癌(MTC)和未分化癌(ATC)4种病理类型,其中PTC是最常见的一种类型,约占85%。近年来,甲状腺癌的发病率呈逐年快速上升趋势。目前,手术、内分泌治疗、核素内放疗是分化型甲状腺癌的三大治疗手段,总体效果良好。但部分甲状腺癌,如碘抵抗远处转移分化型甲状腺癌、低分化癌、未分化癌、远处转移髓样癌等难治性甲状腺癌,预后不良且治疗手段匮乏。免疫治疗近年来逐渐成为研究热点,甲状腺癌的免疫治疗有望成为治疗这部分复杂病例的一种新方法。目前应用于甲状腺癌的免疫治疗方法主要有肿瘤疫苗治疗,免疫检查点抑制剂治疗,过继免疫细胞治疗,单克隆抗体治疗和免疫调节细胞靶向治疗等。     

甲状腺未分化癌的综合治疗

甲状腺未分化癌（ATC）是一种罕见的肿瘤,占甲状腺癌的1%~2%,其死亡病例占甲状腺癌致死病例的大多数。目前,主要采用的治疗方式包括手术、放疗、化疗、靶向治疗和免疫治疗。本文根据最新的美国甲状腺学会（ATA）指南和近年相关文献,阐述ATC的综合治疗方式以提高ATC患者的生存率和生活质量     

胃癌靶向及免疫治疗进展

胃癌是中国常见的消化道恶性肿瘤,具有发病率和死亡率高、进展期患者占比高的特点。既往胃癌的治疗以化疗为主,HER2阳性胃癌可应用曲妥珠单抗。由于胃癌的高度异质性,以致胃癌的药物研发及临床研究进展不尽人意。近几年,随着免疫治疗的进展及新靶点在胃癌中的探索,胃癌治疗取得了重大突破。本文就胃癌靶向和免疫治疗研究进展作简要综述。     

Gastric cancer: The times they are a-changin’

Gastric cancer is the third leading cause of cancer death worldwide. Even though during these last decades gastric cancer incidence decreased in Western countries, it remains endemic and with a high incidence in Eastern countries. The survival in advanced and metastatic stage of gastric cancer is still very poor. Recently the Cancer Genoma Atlas Research Network identified four subtypes with different molecular profiles to classify gastric cancer in order to offer the optimal targeted therapies for pre-selected patients. Indeed, the key point is still the selection of patients for the right treatment, on basis of molecular tumor characterization. Since chemotherapy reached a plateau of efficacy for gastric cancer, the combination between cytotoxic therapy and biological agents gets a better prognosis and decreases chemotherapeutic toxicity. Currently, Trastuzumab in combination with platinum and fluorouracil is the only approved targeted therapy in the first line for c-erbB2 positive patients, whereas Ramucirumab is the only approved targeted agent for patients with metastatic gastric cancer. New perspectives for an effective treatment derived from the immunotherapeutic strategies. Here, we report an overview on gastric cancer treatments, with particular attention to recent advances in targeted therapies and in immunotherapeutic approach.     

Novel approaches in the treatment of thyroid cancer

Although most patients with thyroid cancer do well with traditional therapy, some will go on to develop progressive disease. In the past, few effective treatment options were available for patients with metastatic thyroid carcinoma. However, advances in our understanding of the molecular basis of thyroid cancer initiation and progression have led to many new potential therapies targeted at specific molecular pathways. Many of these novel compounds have been evaluated in cell lines, animal models, and recently, in clinical trials. This review will focus on new potential therapies in the treatment of progressive thyroid cancer, with an emphasis on the activity of these agents in the clinical arena.     

晚期胃癌治疗现状及进展

胃癌是全球范围内常见的恶性肿瘤之一,中国胃癌发病及死亡人数几乎占全球发病和死亡人数的50%。晚期胃癌生存预后差。随着个体化精准治疗的发展,靶向治疗及免疫治疗已成为综合治疗的热点,本文就近年来晚期胃癌的化疗、靶向治疗和免疫治疗研究进展作简要综述。     

Advances in postoperative adjuvant therapy for primary liver cancer

Hepatocellular carcinoma (HCC) is a highly heterogeneous, invasive, and conventional chemotherapy-insensitive tumor with unique biological characteristics. The main methods for the radical treatment of HCC are surgical resection or liver transplantation. However, recurrence rates are as high as 50% and 70% at 3 and 5 years after liver resection, respectively, and even in Milan-eligible recipients, the recurrence rate is approximately 20% at 5 years after liver transplantation. Therefore, reducing the postoperative recurrence rate is key to improving the overall outcome of liver cancer. This review discusses the risk factors for recurrence in patients with HCC radical surgical resection and adjuvant treatment options that may reduce the risk of recurrence and improve overall survival, including local adjuvant therapy (e.g., transcatheter arterial chemoembolization), adjuvant systemic therapy (e.g., molecular targeted agents and immunotherapy), and other adjuvant therapies (e.g., antiviral and herbal therapy). Finally, potential research directions that may change the paradigm of adjuvant therapy for HCC are analyzed.     

Current status of experimental therapeutics for prostate cancer

Hormone refractory prostate cancer (HRPC) is the progression of disease in the presence of castrate serum levels of testosterone with a median survival of approximately 1 year. A variety of strategies have been developed to improve survival for the patients with advanced prostate cancer. Despite such efforts, the effective treatment modality for those patients has not been established other than chemotherapy. New experimental therapeutics such as gene therapy, vaccine therapy and target therapy use various mechanisms to kill tumor cells selectively while sparing surrounding normal tissues. Furthermore, new approaches in the field of chemoprevention are being made. Recent data from landmark studies, in particular vaccines, have shown improvements in overall survival of HRPC patients.     

Advanced Pancreatic Cancer: Flourishing Novel Approaches in the Era of Biological Therapy

The progress in the development of systemic treatment for advanced pancreatic cancer (APC) has been slow. The mainstream treatment remains using chemotherapy including gemcitabine, FOLFIRINOX, and nab‐paclitaxel. Erlotinib is the only approved biological therapy with marginal benefit. Studies of agents targeting epidermal growth factor receptor, angiogenesis, and RAS signaling have not been satisfying, and the usefulness of targeted therapy in APC is uncertain. Understanding in molecular processes and tumor biology has opened the door for new treatment strategies such as targeting insulin‐like growth factor 1 receptor, transforming growth factor β, phosphoinositide 3‐kinase/AKT/mammalian target of rapamycin pathway, and Notch pathway. New directions also include the upcoming immunotherapy and many novel agents that act on the microenvironment. The practice of personalized medicine using predictive biomarkers and pharmacogenomics signatures may also enhance the effectiveness of existing treatment. Future treatment approaches may involve comprehensive genomic assessment of tumor and integrated combinations of multiple agents to overcome treatment resistance.