肿瘤的抗血管生成治疗研究进展

肿瘤治疗已经进入了分子靶向治疗时代。抗血管生成治疗是靶向治疗的重要组成部分,本文回顾分析了近年来肿瘤抗血管生成治疗的最新研究进展情况。     

抗肿瘤血管靶向药物的研究进展

肿瘤血管生成对大多数实体瘤的生长和转移具有重要意义,是多步骤多因素参与的复杂病理过程.选择肿瘤血管生成中的一些关键环节或参与的重要因子作为靶点,研制应用特异性肿瘤血管生成抑制剂或抗体,以靶向调控肿瘤血管生成,控制肿瘤的生长和转移,达到治疗肿瘤的目的.本文对近年来肿瘤血管生成机制和肿瘤血管生成抑制剂的研究进展进行综述.     

血管内皮生长因子与乳腺癌靶向治疗的研究进展

血管形成在乳腺癌的转移中起着重要的作用,血管内皮生长因子(VEGF)是主要的促血管形成因子.抑制血管生成的靶向治疗正在成为治疗乳腺癌的一个新策略,重组人源性抗VEGF单克隆抗体贝伐单抗(rhMAb VEGF、Bevacizumab、Avastin)正是通过抗VEGF作用而抑制肿瘤血管生成.本文就VEGF与乳腺癌靶向治疗的研究进展作一综述.     

血管内皮抑素抗肿瘤研究进展

血管内皮抑素是一种广谱的抗血管生成分子靶向物,其通过抑制肿瘤形成过程的病理性血管生成及抑制肿瘤细胞增殖和转移,发挥抗肿瘤作用。近年来随着靶向治疗药物不断进入临床,血管内皮抑素成为肿瘤综合治疗研究的热点之一。     

纳米脂质体在肿瘤治疗及影像监测中的应用

纳米脂质体作为抗癌药物、治疗基因载体,用于肿瘤靶向治疗和基因治疗,较传统治疗方法能获得更好的疗效.同时包载显像剂对肿瘤细胞和肿瘤血管生成等进行靶向显像,可为了解肿瘤对治疗的反应提供依据.     

小分子抗血管生成药物在乳腺癌中的研究进展

乳腺癌是全世界发病率最高的肿瘤,为女性肿瘤第二大致死病因,内科治疗方法包括化疗、靶向药物治疗及内分泌治疗.化疗联合靶向治疗是恶性肿瘤辅助和晚期治疗的主要手段.血管生成在肿瘤局部进展和转移方面占据重要的地位,成为了一个潜在的治疗靶点.本文主要探讨索拉非尼、舒尼替尼及阿帕替尼这三种小分子酪氨酸激酶类抗血管生成药物在乳腺癌中的研究进展.     

血管生成因子在肿瘤发生发展及转移中作用的研究进展

肿瘤的发生、发展及复发转移离不开肿瘤血管生成。肿瘤血管生成受血管生成刺激因子和血管生成抑制因子的共同调节。通过减少刺激因子生成或增强抑制因子的作用均可抑制血管生成,从而达到抑制肿瘤生长的目的。因此,血管生成因子成为肿瘤治疗研究的靶点,是当前分子靶向治疗研究的基础。     

肿瘤干细胞在肿瘤血管生成中的作用

 肿瘤干细胞（CSC）在肿瘤血管生成中有重要作用,血管生成因子、乏氧等介导了这一过程。CSC能分化成血管内皮细胞,并且参与血管生成拟态的形成,这可能是肿瘤启动和进展的关键因素之一。深入研究CSC在肿瘤血管生成中的作用对肿瘤的靶向治疗有重大意义。     

肿瘤血管内皮细胞异质性分子的研究进展

肿瘤血管与正常血管相比,其发生基础、表现形式及分子表达均存在明显差异,肿瘤血管内皮细胞的分子异质性是肿瘤抗血管生成靶向治疗的理论基础。深入研究肿瘤血管异质性分子对于肿瘤诊断、血管靶向治疗等具有重要意义。本文综述目前肿瘤血管内皮细胞异质性分子的研究进展,为相关研究提供参考。     

超顺磁性氧化铁与肿瘤血管生成磁共振成像和靶向治疗研究

超顺磁性氧化铁(SPIO)具有磁靶向性好、低毒、灵敏和粒子小等特点,可定量评价肿瘤新生血管结构与功能,并可选择性地定位于肿瘤新生血管,发挥抗肿瘤血管生成分子靶向治疗的作用,是医学分子影像学中具有重要作用的选择性磁共振成像对比剂.     

TAMs为靶点的抗肿瘤治疗研究进展

肿瘤微环境与肿瘤细胞通过分子和细胞间的相互作用,在肿瘤的发生发展和转移扩散中具有重要意义。肿瘤相关巨噬细胞（TAMs）作为肿瘤微环境中数量最多的炎症细胞群之一,在肿瘤进展中起到重要作用。肿瘤细胞通过释放多种趋化因子、细胞因子和生长因子招募巨噬细胞,并使其向M2型巨噬细胞类似的特性发展。同时,巨噬细胞释放多种因子,促进肿瘤细胞的生长、血管新生、迁移、侵袭、侵入血管并最终形成远处转移。TAMs在肿瘤组织中的密度与肿瘤患者治疗失败和不良预后密切相关,以TAMs为靶点的抗肿瘤治疗相关研究近年来取得重大进展。在肿瘤发生发展中根据TAMs的作用机制,以TAMs为靶点的抗肿瘤治疗策略是抑制肿瘤微环境中巨噬细胞招募、TAMs生存能力、TAMs表型即由M2型转化为M1型的重塑。本文就TAMs为靶点的抗肿瘤治疗最新进展进行综述。      

The alphaVbeta6 integrin as a novel molecular target for colorectal cancer

Recent advances in the treatment of colorectal cancer have resulted from a shift towards the use of molecular targeting strategies, with the identification of specific antigens critical for the development and progression of these tumors allowing the rational design of new therapeutic agents. The integrin receptor family provides very attractive targets for this 'magic bullet' approach, as they play key roles at all points during the malignant evolution of tumors, influencing growth, progression, angiogenesis and metastasis. One integrin in particular, alphaVbeta6, was recently shown to be upregulated in a model of colorectal tumor progression. Importantly, the consequences of this elevated receptor expression not only impact tumor cell function, but also indicate that alphaVbeta6 is a prognostic variable for colorectal cancer and one that is predictive of patient outcome in early-stage disease. Taken together with its normal expression pattern and known biologic functions, alphaVbeta6 thus emerges as a novel therapeutic candidate.     

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.     

Antiangiogenic combination tumor therapy blocking alpha(v)-integrins and VEGF-receptor-2 increases therapeutic effects in vivo

Anti-angiogenesis is a promising strategy for cancer therapy currently evaluated in clinical trials. The aim of the study was to investigate the effects of an antiangiogenic combination therapy inhibiting alpha(v)-integrins by a c(yclic)RGD-peptide (EMD270179) and blocking VEGFR-2 by SU5416 on tumor angiogenesis and progression in vivo. Experiments were performed in dorsal skinfold chamber preparations of Syrian golden hamsters (60 +/- 5 g) bearing A-Mel-3 tumors. From day 3-10 after tumor-cell implantation, animals (n = 6 per group) were treated by monotherapies using the cRGD-peptide (114 mg/kg/day; i.p.), the VEGFR-2 antagonist (6 mg/kg/day; i.p.) or by the combination of both monotherapies. A control group received only the solvent DMSO. Using intravital microscopy parameters of intratumoral microcirculation were analyzed on day 5, 7 and 10. In separate experiments subcutaneous tumor growth and metastasis formation was evaluated starting therapy on day 0. Functional vessel density was significantly reduced by the combination therapy compared to that by all other groups on day 10. Although intratumoral red blood cell velocity and vessel diameters were less affected, blood flow in vessel segments and the microcirculatory perfusion index were lower after combined therapy compared to controls. In addition, we observed a significantly stronger inhibition of subcutaneous tumor growth and metastasis formation using the combination therapy. These data clearly support the concept of antiangiogenic combination therapy and demonstrate that it may especially be effective when scheduled as an early or prophylactic treatment regimen, thus avoiding angiogenesis-dependent tumor and metastasis initiation or tumor recurrence.     

小分子干扰RNA在头颈部肿瘤的研究进展

以小分子干扰RNA(siRNA)为中心的RNA干扰(RNAi)技术因其高度序列特异性、高效性、作用迅速等特点,越来越来成为恶性肿瘤基因治疗的研究热点.近年来多项研究表明,构建并导入靶向头颈恶性肿瘤相关基因特异siRNA,可以有效地抑制肿瘤的增殖、侵袭,联合其他常规治疗手段可以提高疗效,是头颈肿瘤的基因治疗领域颇有前景的新方法.     

Targeting the eukaryotic translation initiation factor 4E for cancer therapy

The eukaryotic translation initiation factor 4E (eIF4E) is frequently overexpressed in human cancers in relation to disease progression and drives cellular transformation, tumorigenesis, and metastatic progression in experimental models. Enhanced eIF4E function results from eIF4E overexpression and/or activation of the ras and phosphatidylinositol 3-kinase/AKT pathways and selectively increases the translation of key mRNAs involved in tumor growth, angiogenesis, and cell survival. Consequently, by simultaneously and selectively reducing the expression of numerous potent growth and survival factors critical for malignancy, targeting eIF4E for inhibition may provide an attractive therapy for many different tumor types. Recent work has now shown the plausibility of therapeutically targeting eIF4E and has resulted in the advance of the first eIF4E-specific therapy to clinical trials. These studies illustrate the increased susceptibility of tumor tissues to eIF4E inhibition and support the notion that the enhanced eIF4E function common to many tumor types may represent an Achilles' heel for cancer.     

The significance of SUMOylation of angiogenic factors in cancer progression

Angiogenesis is the process of endothelial cell migration and proliferation induced by angiogenic factors, which is essential for the development of tumors. In recent years, studies have reported that SUMOylation acts on tumor angiogenesis by targeting angiogenic factors as one of post-translational modifications of proteins. Anti-angiogenic therapy is a new treatment method for tumor treatment following radiotherapy and chemotherapy, and it inhibits tumor growth by blocking tumor blood vessels. Therefore, SUMOylation may become a potential target for anti-angiogenesis therapy. This article focuses on the effect of SUMOylation on vascular growth factors, important signaling pathways proteins, and the migration and function of endothelial cells, in order to provide a new research idea for the anti-angiogenic therapy of tumors.     

Novel therapeutic approaches for targeting tumor angiogenesis

Current attempts to disrupt the complex process of tumor blood vessel formation are predominantly focused on targeting the vascular endothelial growth factor (VEGF)-VEGFR signaling pathway. Although clinically proven to inhibit VEGF and its receptors, these pharmacologic agents are selective, but not specific. Consequently, many of the approved inhibitors also impair other molecular targets leading to increased toxicity. Current efforts to unravel the complexity of tumor angiogenesis have identified several new candidates for antivascular therapy. In this review article, we identify well-established and novel angiogenic molecules and discuss benefits of the therapeutic approaches based on targeting of such factors.     

Antiangiogenic effects of zoledronate on cancer neovasculature

Angiogenesis, one of the hallmarks of cancer, supplies nutrients to cancerous tissues to facilitate rapid growth. Targeting cancer-associated angiogenesis is an important goal in cancer therapy and there are currently many drugs that affect tumor-associated vasculature. In this article, we will focus on the antiangiogenic effects of zoledronate (ZA), a bisphosphonate drug routinely used in the treatment of cancer-associated bone disease. This article covers the known effects of ZA throughout the clinical process. It also covers the animal models of cancer that have been treated with ZA and evaluated for angiogenes is, concluding with the current clinical data pertaining to angiogenic factors after ZA treatment.     

Arginine deiminase and other antiangiogenic agents inhibit unfavorable neuroblastoma growth: potentiation by irradiation

In spite of aggressive therapy, children suffering from neuroblastoma have a poor prognosis. Therapeutic failure is most often observed in neuroblastomas with unfavorable features, including amplification/over-expression of the N-myc oncogene, rapid growth, effective angiogenesis and/or the tendency to metastasize. Here, we have used cultured human neuroblastoma cells with such features and we have examined whether antiangiogenic agents alone or in combination with tumor irradiation inhibit their angiogenesis and growth in vivo. We report that antiangiogenic agents (arginine deiminase, SU5416 and DC101) inhibit in vivo growth of neuroblastomas with unfavorable properties and that these effects are potentiated by simultaneous irradiation. Combination of either agent with irradiation leads to a reduction in the absolute number of tumor vessels and of perfused tumor vessels. Combination of arginine deiminase or DC101 with irradiation does not increase tumor hypoxia. Our data demonstrate for the first time that arginine deiminase suppresses the growth of unfavorable experimental neuroblastomas and that this effect is potentiated by irradiation. We suggest that antiangiogenesis alone or in combination with established therapeutic regimen may improve the outcome of unfavorable neuroblastomas in a clinical setting.