抗血管生成药物致高血压的降压治疗的合理用药

高血压是抗血管生成药物常见不良反应之一,多为轻、中度。一般通过标准降压治疗即可控制,而严重者可影响患者的抗肿瘤疗效果甚至中断靶向药物治疗。因此,合理选择降压药物对于患者的抗肿瘤治疗具有重要意义。笔者主要探讨抗血管生成药物致高血压的降压药物选择,以期为临床用药提供参考。     

抗肿瘤类药物在眼科疾病的临床应用及研究进展

抗肿瘤药物具有抑制细胞生长、抑制增殖代谢、抑制新生血管生成等特殊作用,使其在眼科疾病中得到应用,早先仅应用于眼科肿瘤的治疗,后来应用于青光眼、翼状胬肉的治疗,近年来抗新生血管靶点类药物的兴起,使抗肿瘤类药在眼科的应用范围更加广泛,主要通过抑制新生血管、减轻视网膜水肿来提高患者视力。现就近年来,抗肿瘤药物在抗增殖代谢、抗新生血管生成的眼部相关疾病中的临床应用及研究进展进行简要概述。     

分子影像技术在抗肿瘤药物研发中的应用进展

目的:为借助分子影像技术提高抗肿瘤药物研发效率、降低研发成本提供参考。方法:以"分子影像技术""药物研发""肿瘤诊断""生物标志物"等为关键词,通过检索和筛选中国知网、中国国家图书馆、PubMed、Web of Science等数据库收录的2017年4月以前发表的分子影像技术用于抗肿瘤药物研发的最新文献,进行整理、归纳和综述。结果与结论:近年来分子影像技术已取得重大进展,正越来越广泛地应用于抗肿瘤药物研发,并在药物生物分布标志物(药物由血液循环运送到体内各脏器的过程)、药效学生物标志物(药物对机体的作用及作用机制)、疾病生物标志物(用于疾病诊断、判断疾病分期或者用来评价新药或新疗法在目标人群中的安全性及有效性)及患者选择生物标志物(识别可能对治疗有反应的患者,指导治疗)等方面发挥重要作用。分子影像技术的成功应用,有望提高抗肿瘤药物开发全链条的效率和收益,其潜在价值有待进一步开发。     

分子靶向抗肿瘤药物十年历程启迪

本文综合分析近十年来分子靶向抗肿瘤药物的历程,回顾各类分子靶向抗肿瘤药物的特点,提出分子靶向抗肿瘤药物开发中值得关注的几个问题:如药物的毒副作用、耐受性,个体化治疗与生物标志物,以及预测敏感患者生物标志物研究等。     

靶向药物及中药抗血管治疗乳腺癌研究进展

目的叙述靶向药物及抑制血管生成中药治疗乳腺癌的近年研究进展。方法通过收集大量关于靶向药物治疗乳腺癌及抑制血管生成中药治疗乳腺癌相关文献。结果大量实验研究表明肿瘤血管生成和乳腺癌演进密切相关。抗血管生成药物对乳腺癌的治疗有广阔的应用前景。与其他新疗法类似,抗血管生成靶向药物的疗效的评价尚需设计严谨的前瞻性临床随机试验来加以证实。结论抗血管生成治疗肿瘤和转移已成为肿瘤生物靶向治疗研究的主要方向。中药抗血管生成药物在乳腺癌治疗也取得一定的进展及成果,但仍需要进一步研究,发挥其优势为预防及治疗肿瘤提供新的途径。     

血管内皮生长因子受体及其小分子抑制剂的研究进展

目前抗血管生成治疗是抗肿瘤研究的热点.血管内皮生长因子(VEGF)是刺激血管生成的重要因子之一,血管内皮生长因子受体(VEGFR)在肿瘤新生血管中高表达,因此成为肿瘤靶向治疗的理想靶点.以VEGF、VEGFR为靶点的抗肿瘤药物除了常见的单克隆抗体药物阿伐斯汀外,小分子抑制剂舒尼替尼、索拉非尼等也已经广泛使用;另外,一些...     

肿瘤抗血管生成疗法及相关药物的研究进展

目的介绍肿瘤抗血管生成疗法的作用机制及近年抗血管生成药物研究进展。方法根据国内外的文献资料,进行整理归纳。结果肿瘤血管生成主要与生长因子、溶解酶及炎症细胞特异性分子表达增加有关。研究证明许多天然或人工合成化学分子通过作用于上述血管增生反应中的特异性分子发挥抗肿瘤效应。结论抗血管生成药物有望成为新一代抗肿瘤药。     

肿瘤抗血管生成疗法及相关药物的研究进展

目的 介绍肿瘤抗血管生成疗法的作用机制及近年抗血管生成药物研究进展。方法根据国内外的文献资料，进行整理归纳。结果 肿瘤血管生成主要与生长因子、溶解酶及炎症细胞特异性分子表达增加有关。研究证明许多天然或人工合成化学分子通过作用于上述血管增生反应中的特异性分子发挥抗肿瘤效应。结论 抗血管生成药物有望成为新一代抗肿瘤药。     

舒尼替尼治疗晚期胃肠间质瘤18例不良反应护理

舒尼替尼是一种多靶点的生物靶向抗肿瘤药物,能同时抑制多条信号传导通路,具有抗肿瘤和抗血管生成作用,在肾细胞癌和胃肠间质瘤的临床前和临床研究中均显示出确切的抗肿瘤效应。其在治疗过程中会出现不良反应,常见的有胃肠道反应、手足综合征、口炎、发色改变、高血压、骨髓抑制等,现将护理情况报告如下。1临床资料     

肿瘤血管生成机制及抗肿瘤血管新生的靶向药物研究进展

抗肿瘤血管新生治疗是以血管内皮细胞为靶点,通过降低血管活性因子的活性、抑制内皮细胞增殖和迁移、改变肿瘤生长微环境,从而抑制肿瘤生长过程中的血管新生,切断肿瘤的供养,最终达到遏制肿瘤生长和转移的目的,是一种全新的靶向肿瘤治疗方法.该方法具有高效特异性、不易产生耐药性、药物易于到达靶部位和毒副作用小等优点,可以有效地抑制肿瘤的转移和复发,现在已成为抗肿瘤血管生成药物研究的热点之一,该文综述了肿瘤血管生成的机制及抗血管新生治疗药物的最新研究进展.     

Is the toxicity of anti-angiogenic drugs predictive of outcome? A review of hypertension and proteinuria as biomarkers of response to anti-angiogenic therapy

INTRODUCTION: The prototypic anti-angiogenic agents, VEGF inhibitors, are increasingly used in clinical practice to treat a variety of tumours. Although generally well tolerated, their toxicities can be significant or occasionally life threatening. The ability to identify those patients whose disease will respond to VEGF inhibitors would minimise exposure to ineffective drugs for some patients. To date, there are no validated predictive or prognostic biomarkers for anti-angiogenic drugs. Toxicities such as hypertension and proteinuria are related to the effect of VEGF inhibition on the vasculature. This has led to the investigation of these toxicities as potential biomarkers of clinical outcome in patients treated with these agents. AREAS COVERED: Putative mechanisms for the development of hypertension and proteinuria, and their potential role as clinically useful biomarkers in relation to anti-angiogenic drugs are discussed in this article. PUBMED, EMBASE and abstracts presented at the American Society of Clinical Oncology until July 2011 were searched to identify relevant English language articles. Studies of anti-angiogenic therapies testing the relationship of either hypertension or proteinuria with outcome were included. EXPERT OPINION: The evidence in support of the hypothesis that hypertension and proteinuria are biomarkers of response to anti-angiogenic drugs is inconclusive. Current evidence suggests that hypertension is a pharmacodynamic effect of anti-angiogenic agents. Future studies should aim to measure and report toxicities in a standardised manner to facilitate comparisons between studies.     

Molecular and cellular biomarkers for angiogenesis in clinical oncology

Medical oncologists are increasingly using anti-angiogenic drugs, but identifying the best-suited drug and the optimal dosage and schedule for treatment of patients remain challenging issues. Circulating endothelial cells (CECs) and circulating endothelial progenitors (CEPs) are modulated in a variety of diseases including cancer, and are promising surrogate biomarkers in oncology. Molecular surrogate markers, on the other hand, are more scanty at the present time, because the identification of truly endothelial cell-restricted genes and/or antigens is complex. Here, we discuss the biological and technical facets of the search and validation of new biomarkers for angiogenesis.     

Anti-VEGF and beyond: shaping a new generation of anti-angiogenic therapies for cancer

The anti-angiogenic class of drugs is one of the few where representatives have gained international approval for clinical use in oncology during the past decade. Most of the biological and clinical activity of the currently available generation of anti-angiogenic drugs targets vascular endothelial growth factor (VEGF) and its related pathways. However, the clinical benefits associated with the use of these drugs have, so far, been limited. There is, therefore, an unmet need for biomarkers that can be used to identify patients who are most likely to benefit therapeutically and also to predict the best schedule and dosage for these drugs. Here, we discuss some of the emerging new combination strategies involving the approved anti-angiogenic drugs, some of the emerging targets associated with neoplastic angiogenesis and some novel agents used as a paradigm of the next generation of anti-angiogenic drugs.     

Tumor endothelial markers as a target in cancer

Introduction: Several anti-angiogenic agents have been developed and some of them have been clinically applied in the tumor therapy. Anti-angiogenic therapy faces some hurdles: inherent or acquired resistance, increased invasiveness, and lack of biomarkers. Characterization of tumor endothelial markers may help to target endothelium and to identify potential predictive factors of response to anti-angiogenic therapies. Numerous surrogates, angiogenic and endothelium markers have emerged from recent pre-clinical studies, including physiological and soluble molecules in plasma and from platelets, circulating cells, tumor tissue factors and imaging markers. However, no wholly validated biomarkers currently exist to predict the success or the failure of the anti-angiogenic therapy of cancer. Therefore, the research of suitable and validate biomarkers is currently ongoing.

Areas covered: This review provides an overview of the status of our knowledge concerning tumor endothelial markers, therapeutics targeting, possible resistance mechanisms and predictive value of these biomarkers and discuss future strategies to use and identify them in the anti-angiogenic therapy.

Expert opinion: Anti-angiogenesis is a milestone to improve the treatment of several types of cancer and predictive biomarkers for a response to anti-endothelium therapy are one of the most important challenges for anti-angiogenesis research.     

Targeting angiogenesis for the treatment of prostate cancer

INTRODUCTION: While multiple therapies exist that prolong the lives of men with advanced prostate cancer, none are curative. This had led to a search to uncover novel targets for prostate cancer therapy, distinct from those of traditional hormonal approaches, chemotherapies, immunotherapies and bone-targeting approaches. The process of tumor angiogenesis is one target that is being exploited for therapeutic gain. AREAS COVERED: The most promising anti-angiogenic approaches for treatment of prostate cancer, focusing on clinical development of selected agents. These include VEGF-directed therapies, tyrosine kinase inhibitors, tumor-vascular disrupting agents, immunomodulatory drugs and miscellaneous anti-angiogenic agents. While none of these drugs have yet entered the market for the treatment of prostate cancer, several are now being tested in Phase III registrational trials. EXPERT OPINION: The development of anti-angiogenic agents for prostate cancer has met with several challenges. This includes discordance between traditional prostate-specific antigen responses and clinical responses, which have clouded clinical trial design and interpretation, potential inadequate exposure to anti-angiogenic therapies with premature discontinuation of study drugs and the development of resistance to anti-angiogenic monotherapies. These barriers will hopefully be overcome with the advent of more potent agents, the use of dual angiogenesis inhibition and the design of more informative clinical trials.     

Anti-angiogenic drug discovery: lessons from the past and thoughts for the future

INTRODUCTION: Since the pioneering work of Judah Folkman, the discovery of bevacizumab has introduced the use of anti-angiogenic agents as a new modality for the treatment of cancer. Currently, hundreds of clinical trials involving anti-angiogenic agents, targeting different elements of the tumour angiogenesis pathway, are underway. However, thus far, the benefits of anti-angiogenic therapy in unselected patient populations are often marginal with harmful side effects. AREAS COVERED: This article presents a detailed discussion of the lessons learnt from the use of bevacizumab and other VEGF pathway inhibitors in the clinical setting. Specifically, this article provides a review of the literature on anti-VEGF agents and other angiogenesis inhibitors used in pre-clinical and clinical trials for cancer treatment. EXPERT OPINION: Future anti-angiogenic drug design centres on multiple protein targets and combinations including: growth factors, hypoxia-inducible factor and tumour endothelial cell markers unique to the tumour vasculature. Furthermore, treatment dosing, scheduling and combination with radiation and chemotherapy require further investigation, as does the potential of treating early disease, and the development of biomarkers which accurately predict response to therapy. These are essential for the future development of these drugs with individualised therapy likely to be the ultimate goal.     

Anti-angiogenic therapies for malignant pleural mesothelioma

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a disease with a dismal prognosis. Currently available treatments have modest results. Therefore, new agents and new treatment strategies are eagerly awaited by patients and clinicians. Preclinical and clinical studies have shown that angiogenesis plays a very important role in MPM. Therefore, a great hope has been placed in the use of anti-angiogenic agents in this disease. AREAS COVERED: Studies regarding anti-angiogenic treatments in MPM with bevacizumab, tyrosine-kinase inhibitors (TKIs) and other agents were critically analyzed, with an overview of ongoing trials and future perspectives, including research on biomarkers. EXPERT OPINION: The clinical use of angiogenesis inhibitors in MPM patients has resulted more challenging than anticipated. The intrinsic complexity of neo-angiogenesis, and its redundant regulatory mechanisms, suggests that multiple and different biomarkers are needed to predict efficacy of anti-angiogenic agents and to monitor their biological and therapeutic effects. The growing understanding of the molecular alterations and key pathways that underlie the resistance to VEGF inhibitors will allow to design studies of the combination of agents targeting these pathways with anti-VEGF therapies. Only a tight integration of preclinical and clinical studies will allow to achieve a real progress in MPM patients with this therapeutic strategy.     

349例药品不良反应报告分析

目的：考察药品不良反应（ADR）发生情况,分析ADR发生的特点与规律,促进,临床合理用药。方法：采用回顾性方法,对2009年1-8月上报的349份ADR报告,按患者年龄、性别、给药途径、引起ADR的药品种类、涉及器官／系统以及临床表现和ADR转归与评价等进行分析。结果：349例ADR报告中,涉及药品11类159种;ADR报告中,女性46．42％（162／349）,男性53．58％（187／349）;静脉给药ADR83．09％（290／349）;抗感染药物39．54％（138／349）,其中氟喹诺酮ADR28.26％（39／138）,左氧氟沙星5．73％（20／138）。抗肿瘤药物与心血管系统31．80%（111／349）。ADR的临床表现中,皮肤及附件损害为主要症状;ADR多为一般性（90．27％）,并且转归良好。结论：本组ADR的发生无明显性别差异;静脉给药较其他给药途径易发生ADR抗感药物引发的ADR最高,其次为抗肿瘤药与心血管系统用药。     

Anti-angiogenic drug discovery: lessons from the past and thoughts for the future

Introduction: Since the pioneering work of Judah Folkman, the discovery of bevacizumab has introduced the use of anti-angiogenic agents as a new modality for the treatment of cancer. Currently, hundreds of clinical trials involving anti-angiogenic agents, targeting different elements of the tumour angiogenesis pathway, are underway. However, thus far, the benefits of anti-angiogenic therapy in unselected patient populations are often marginal with harmful side effects.

Areas covered: This article presents a detailed discussion of the lessons learnt from the use of bevacizumab and other VEGF pathway inhibitors in the clinical setting. Specifically, this article provides a review of the literature on anti-VEGF agents and other angiogenesis inhibitors used in pre-clinical and clinical trials for cancer treatment.

Expert opinion: Future anti-angiogenic drug design centres on multiple protein targets and combinations including: growth factors, hypoxia-inducible factor and tumour endothelial cell markers unique to the tumour vasculature. Furthermore, treatment dosing, scheduling and combination with radiation and chemotherapy require further investigation, as does the potential of treating early disease, and the development of biomarkers which accurately predict response to therapy. These are essential for the future development of these drugs with individualised therapy likely to be the ultimate goal.     

Microtubule-targeting agents in angiogenesis: where do we stand?

Angiogenesis is a key event of tumor progression and metastasis and hence a target for cancer chemotherapy. Therapeutic strategies focused on angiogenesis include the discovery of new, targeted anti-angiogenic agents and the re-evaluation of conventional anti-cancer drugs. Here, we review the most recent studies investigating the molecular and cellular mechanisms responsible for the anti-angiogenic activity of microtubule-targeting agents (MTAs). These agents include some of the most widely used and effective antitumor drugs that are also among the most anti-angiogenic. In addition, we summarize the latest results of pre-clinical and clinical studies involving MTAs administered at low metronomic doses and in anti-angiogenic combination strategies. Finally, we discuss the future development of these agents, their clinical potential and their limitations.