超声微泡在肝癌治疗中的应用研究进展

随着超声治疗学的兴起及分子影像技术的深入发展，超声微泡除了可以增强病灶的显像，还能作为一种新型的药物或基因的载体，通过靶向传递药物或基因，以达到治疗疾病的目的。超声微泡载药物或基因的靶向传递，已成为一种新型的肿瘤治疗技术，它不仅具有无辐射、安全、高效、易重复使用的优点，还为药物或基因的靶向释放提供了技术支持，在肝癌的治疗研究中展现出良好的前景，有望为肝癌患者提供新的治疗思路。本文就超声微泡在肝癌治疗中的机制与应用，以及存在的问题进行综述。     

原发性肝癌分子靶向治疗临床研究进展

随着分子生物学技术的发展,分子靶向治疗已成为21世纪肿瘤治疗的主要方向和潮流.针对VEGF/VEGFR、EGFR、Raf-MAPK-ERIC、HGFR等靶点的分子靶向治疗以及与其他治疗的联合治疗开始用于原发性肝癌的临床,并在一些临床试验中取得了令人鼓舞的结果.针对原发性肝癌的分子靶向治疗的临床研究进展进行综述.     

索拉非尼治疗原发性肝癌的研究进展

原发性肝癌是我国高发常见的恶性肿瘤，起病隐袭，早诊困难，确诊时大多数已达局部晚期或远处转移，治疗棘手，预后很差；常规化疗药物的作用有限，没有证据显示有明显的生存获益。已知肝癌的发病机制十分复杂，其发生、发展和转移与多种基因突变、细胞信号传导通路和新生血管增生异常密切相关，其中存在着多个关键性环节，正是采用分子靶向治疗的理论基础和潜在的靶点。近年来，应用分子靶向药物治疗肝癌的研究逐渐受到重视，正在成为新的热点，而多靶点、多激酶抑制剂索拉非尼（多吉美）作为代表性药物，已经取得突破性成果，能够有效地延长晚期患者的生存时间，开创了肝癌靶向治疗的新时代。为了尽快地熟悉了解有关动态，本文全面而系统地综述了索拉非尼治疗肝癌的实验研究、临床上单药和联合治疗研究的新进展，并讨论展望了未来的发展方向。     

肝癌单克隆抗体制备及应用

肝癌单克隆抗体是近年来治疗肝细胞癌(HCC)的重要辅助方法之一，其制备方法的完善和改进促进了对肝癌相关抗原的检测诊断，以及与治疗药物偶联的靶向应用。现综述肝癌单克隆抗体的制备技术和应用于肝癌治疗的最新研究进展。     

肝癌的分子靶向治疗研究进展

不能手术和已转移的原发性肝细胞癌预后很差,放化疗难以使患者受益。近年来,分子靶向治疗对一些肿瘤已取得突破性进展,肝癌的分子靶向治疗也在临床试验中取得了令人鼓舞的结果。目前的肝癌临床研究主要针对EGFR、VEGF/VEGFR、Raf/MAPK-ERK、HGF、乙肝表面抗原等靶点。本文针对肝癌的分子靶向治疗的研究进展进行了综述。     

中晚期肝细胞肝癌的靶向治疗动态

目的:总结近年来国内外对中晚期肝细胞肝癌靶向治疗的研究进展.方法:应用计算机检索CHKD期刊全文数据库及PubMed检索系统,以"肝细胞肝癌"和"治疗进展"为关键词检索2007-01-2009-11相关肝细胞肝癌中晚期治疗进展的文献.纳入标准:1)肝细胞肝癌的病因、分布及分子生物学形成机制;2)原发性肝癌的分期研究及对治疗的指导;3)肝细胞肝癌的靶向、化疗及免疫治疗理念进展.根据纳入标准纳入分析24篇文献.结果:针对肝细胞肝癌肿瘤血管形成机制及多信号转导途径的分子靶向治疗被证实为可以有效延长患者生存期.成为中晚期肝细胞肝癌治疗新方向.结论:靶向药物相互联合或联合化疗成为治疗趋势;探讨对索拉非尼等药物的相对特异的生物学标志可更好地筛选敏感治疗人群.     

纳米铁核素靶向治疗肝癌的内照射吸收剂量估算

目的：探讨放射性核素内照射治疗肝癌时核素的选取以及如何减少核素辐射对身体的副作用。方法：选取衰变时发射β射线的纳米铁核素，在外加旋转磁场作用下靶向定位到肝组织。结果：从理论上估算纳米铁核素靶向治疗肝癌时，肝组织的平均吸收剂量。结论：纳米铁核素在外加旋转磁场作用下，少量核素即能对肝组织产生较大的辐射，对其它器官并无副作用，能达到治疗肝癌的目的。     

靶向超声微泡在肝癌治疗领域的研究进展

在临床上现有的肝癌治疗方法为手术切除、射频消融、动脉栓塞化疗、无水酒精瘤内注射及肝移植等。靶向超声微泡的出现,拓展了传统肝癌的治疗思路,它不仅具有无创伤、无痛苦、无辐射、易重复使用的优点,还为药物和基因的靶向释放提供技术支持,并可以明显增强现有治疗方法的效果,在肝癌治疗方面展示出十分诱人的前景。本文就目前靶向超声微泡在肝癌治疗领域的机制与应用,以及存在的局限性和发展做一综述。     

肝癌靶向药物治疗的研究进展

肝癌的分子靶向治疗具有较好的分子选择性,能高效并选择性地杀伤肿瘤细胞．减少对正常组织的损伤。目前肝癌的靶向药物治疗主要有以下几种：肝细胞生长因子及其受体抑制剂、多靶点激酶抑制剂、抗血管内皮生长因子（VEGF）药物、表皮生长因子受体抑制剂、DNA甲基化抑制剂、环氧化酶-2抑制剂、Nuclerfactor—kappaB（NF—κB）路径靶向药物、细胞周期控制药物等。全文对肝癌靶向药物治疗的研究进展作一综述。     

肝癌的靶向治疗

肝癌（HCC）是全球最富有挑战性的恶性肿瘤之一。HCC需要综合治疗，目前尚无特效的治疗药物。分子靶向药物的发展，使HCC的全身治疗有了新的希望。阐述了分子靶向药物的现状，多激酶抑制剂、抗血管生成和抗表皮生长因子受体药物在临床上的进展，认为索拉芬尼是晚期HCC的新的标准治疗药物。     

肿瘤联合治疗的时代

多种治疗方法的联合能够提高肿瘤的治疗效果,这是一个肿瘤联合治疗的时代。联合治疗策略包括免疫治疗为基础的联合治疗、微生物治疗实现肿瘤个体化治疗、细胞周期联合治疗、不同靶向药物的联合和化疗联合治疗。多种系统治疗方法的联合也是肿瘤治疗的未来方向。     

The Role of the Insulin-like Growth Factor-1 Receptor (IGF-1R), Phosphatase and Tensin Homolog (PTEN), c-Met, and the PI3-Kinase Pathway in Colorectal Cancer

Colorectal cancer (CRC) is the second-leading cause of cancer deaths in the US and the third most common cancer malignancy annually. Overall prognosis of metastatic CRC is still poor, with five-year survival within 5?C8?%. Previous molecular studies of CRC established several key events in CRC disease progression, including APC inactivation, ??-catenin activation, and activating KRAS and BRAF mutations. More recent development of molecular therapeutics has led to the current use of anti-EGFR monoclonal antibody in targeted therapy of advanced CRC. Also, high-throughput cancer genome mutational analysis and newer second-generation cancer genome sequencing have, in recent years, resulted in a deeper understanding of the genome and of regulation of CRC. Most importantly, improved understanding of the involvement of many of the novel molecular targets in CRC tumorigenesis and tumor progression would engender the development of novel targeted therapeutics to treat the disease. Moreover, studies in molecular determinants of predictive and prognostic biomarkers of targeted therapy would further enable better strategies for the use of targeted therapeutics in preventing or overcoming treatment resistance. In this review, we focus on recent findings and their clinical relevance to actionable molecular targets??insulin-like growth factor-1 receptor (IGF-1R), phosphatase and tensin homolog (PTEN), c-Met and phosphatidylinositol 3-OH kinase (PI3-K)??in CRC personalized cancer therapeutics.     

CDK4/6抑制剂的联合治疗模式

 细胞周期素依赖激酶（CDKs）抑制剂联合内分泌治疗已经用于晚期乳腺癌的治疗。除了内分泌治疗，CDK4/6抑制剂还可以联合表皮生长因子受体（EGFR）抑制剂、磷脂酰肌醇-3激酶（PI3K）/哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂、化学治疗、免疫治疗、分子靶向治疗和其他治疗。联合治疗模式克服了CDK4/6抑制剂的耐药并提高了临床疗效，开启了肿瘤精准治疗的一扇新窗口。     

Integration of targeted therapies in gemcitabine chemotherapy regimens

Lung cancer is one of the most common malignancies in the United States and the most lethal. Non-small-cell lung cancer (NSCLC), which accounts for over 80% of all lung cancer cases, results in a particularly poor prognosis and a high mortality rate. The 5-year survival rate is still only 15%, and most patients ultimately die from this disease. Unfortunately, the therapeutic improvements resulting from the new generation of cytotoxic agents seems to have reached a plateau. Targeted therapeutics, or agents aimed at specific biologic pathways, represent a potential for great improvements in survival from this disease. Because of their greater specificity, targeted therapeutics have the potential for decreased toxicity and increased efficacy. The main categories of targeted therapies applicable for NSCLC include receptor-targeted therapy, signal transduction or cell-cycle inhibition, angiogenesis inhibition, gene therapy, and vaccines. These new agents are, in theory, more target-specific, less toxic, easier to administer, and may lead to enhanced safety and survival for patients with advanced NSCLC. Targeted therapies are in different phases of clinical testing and have shown encouraging activity as single agents or in combination with chemotherapy as well as radiation therapy. Herein we explore targeted therapy in combination with gemcitabine.     

The role and target potential of protein tyrosine phosphatases in cancer

Protein tyrosine phosphatases (PTPases) are attractive targets for developing novel cancer therapeutics. Activated via gain-of-function point mutations or overexpression, several PTPases have been identified as critical oncogenic molecules in human malignancies that may be targeted with small chemical inhibitors as a therapeutic strategy. Tumor suppressor PTPases have also been discovered as contributing factors in cancer development that may be targeted via intervention of downstream signaling events for therapeutic purposes. In addition, PTPases have been identified as key negative regulators of cytokines or immune cells. Targeting these negative PTPases may improve the efficacy of cytokine therapy and immunotherapy, which currently have modest response rates and limited survival benefit. Inhibitors of selective PTPases have demonstrated significant preclinical antitumor activity, leading to early-phase clinical trials. Further research and development could lead to PTPase-targeted cancer therapeutics in the near future.     

Protein kinase Calpha and epsilon small-molecule targeted therapeutics: a new roadmap to two Holy Grails in drug discovery?

Protein kinase (PK)Calpha and epsilon are rational targets for cancer therapy. However, targeted experimental therapeutics that inhibit PKCalpha or epsilon are unavailable. The authors established recently that covalent modification of an active-site cysteine in human PKCepsilon, Cys452, by small molecules, for example 2-mercaptoethanolamine, is necessary and sufficient to render PKCepsilon kinase-dead. Cys452 is conserved in only eleven human protein kinase genes, including PKCalpha. Therefore, the design of small molecules that bind PKC active sites with an electrophile substituent positioned proximal to the Cys452 side chain may lead to targeted therapeutics that selectively inhibit PKCepsilon, PKCalpha or other PKC isozymes.     

乳腺癌内分泌治疗加时代

激素受体（HR）阳性乳腺癌对内分泌治疗有效但也会产生耐药,以内分泌治疗为基础的联合治疗克服了耐药并提高了内分泌治疗的效果。乳腺癌的治疗已进入内分泌治疗加时代,这包括乳腺癌内分泌治疗联合分子靶向药物、血管生成抑制剂、磷脂酰肌醇-3激酶（PI3K）抑制剂、哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂、细胞周期素依赖激酶（CDK)4/6抑制剂、抗HER2剂和表观遗传调节剂。本文系统总结乳腺癌内分泌联合治疗的临床研究结果和潜在药物。     

Indium-111 capromab pendetide in the management of recurrent prostate cancer

Protein kinase (PK)Cα and ε are rational targets for cancer therapy. However, targeted experimental therapeutics that inhibit PKCα or ε are unavailable. The authors established recently that covalent modification of an active-site cysteine in human PKCε, Cys452, by small molecules, for example 2-mercaptoethanolamine, is necessary and sufficient to render PKCε kinase-dead. Cys452 is conserved in only eleven human protein kinase genes, including PKCα. Therefore, the design of small molecules that bind PKC active sites with an electrophile substituent positioned proximal to the Cys452 side chain may lead to targeted therapeutics that selectively inhibit PKCε, PKCα or other PKC isozymes.     

Clinical development of new molecular targeted therapeutics for cancer therapy

Recently much attention has been paid to clinical development of new drugs targeting the important molecules involved in cell growth, motility, invasion, metastatic formation of cancer cells and tumor angiogenesis. Among them, several drugs are designed to inhibit those activities, by which cancer growth and/or metastasis may be controlled. A major problem in developing new molecular targeted therapeutics is determining the optimal biological dose in Phase I studies. Appropriate surrogate markers should be employed to evaluate their therapeutic efficacy before entering the Phase III study. A future strategy to evaluate the efficacy of new drugs in combination with conventional anticancer therapy (surgery, radiotherapy and chemotherapy) is required. For this, careful consideration must be given to the design of clinical Phase III trials. This paper discusses the present status and future strategy for development of new molecular targeted therapeutics in clinics.