-
Eye (London, England) Jun 2018Clinical efficacy of intravitreal anti-VEGF drugs has been widely demonstrated in several angiogenesis-driven eye diseases including diabetic macular edema and the... (Review)
Review
Clinical efficacy of intravitreal anti-VEGF drugs has been widely demonstrated in several angiogenesis-driven eye diseases including diabetic macular edema and the neovascular form of age-related macular degeneration. Pegaptanib, ranibizumab, and aflibercept have been approved for use in the eye, whereas bevacizumab is widely used by ophthalmologists to treat patients "off-label". These drugs are active in the nanomolar to picomolar range; however, caution is required when establishing the rank order of affinity and potency due to in vitro inter-experimental variation. Despite the small doses used for eye diseases and the intravitreal route of administration may limit systemic side effects, these drugs can penetrate into blood circulation and alter systemic VEGF with unknown clinical consequences, particularly in vulnerable groups of patients. Clinical pharmacokinetics of ocular anti-VEGF agents should therefore be taken into account when choosing the right drug for the individual patient. The gaps in current understanding that leave open important questions are as follows: (i) uncertainty about which drug should be given first, (ii) how long these drugs can be used safely, and (iii) the choice of the best pharmacological strategy after first-line treatment failure. The current review article, based on the information published in peer-reviewed published papers relevant to anti-VEGF treatments and available on the PubMed database, describes in detail the clinical pharmacology of this class of drugs to provide a sound pharmacological basis for their proper use in ophthalmology clinical practice.
Topics: Angiogenesis Inhibitors; Humans; Retina; Retinal Diseases; Vascular Endothelial Growth Factor A
PubMed: 29398697
DOI: 10.1038/s41433-018-0021-7 -
Drug Discovery Today Feb 2018Zebrafish, an amenable small teleost fish with a complex mammal-like circulatory system, is being increasingly used for drug screening and toxicity studies. It combines... (Review)
Review
Zebrafish, an amenable small teleost fish with a complex mammal-like circulatory system, is being increasingly used for drug screening and toxicity studies. It combines the biological complexity of in vivo models with a higher-throughput screening capability compared with other available animal models. Externally growing, transparent embryos, displaying well-defined blood and lymphatic vessels, allow the inexpensive, rapid, and automatable evaluation of drug candidates that are able to inhibit neovascularisation. Here, we briefly review zebrafish as a model for the screening of anti(lymph)angiogenic drugs, with emphasis on the advantages and limitations of the different zebrafish-based in vivo assays.
Topics: Angiogenesis Inhibitors; Animals; Drug Evaluation, Preclinical; Humans; Models, Animal; Neovascularization, Pathologic; Zebrafish
PubMed: 29081356
DOI: 10.1016/j.drudis.2017.10.018 -
International Journal of Molecular... May 2015Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate... (Review)
Review
Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G2/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms.
Topics: Angiogenesis Inhibitors; Animals; Breast; Breast Neoplasms; Female; Genistein; Humans; Isoflavones; Neovascularization, Pathologic; Signal Transduction; Glycine max
PubMed: 26006245
DOI: 10.3390/ijms160511728 -
Journal of Hematology & Oncology Oct 2016Monoclonal antibodies and small molecule tyrosine kinase inhibitors (TKIs) directed against the vascular endothelial growth factor (VEGF) or its receptors have been... (Meta-Analysis)
Meta-Analysis Review
Monoclonal antibodies and small molecule tyrosine kinase inhibitors (TKIs) directed against the vascular endothelial growth factor (VEGF) or its receptors have been investigated in several studies for the treatment of advanced gastric cancer (GC). In the present study, we aimed to evaluate the efficacy and safety of angiogenesis inhibitors in advanced GC. We searched published randomized controlled trials (RCTs) comparing angiogenesis inhibitors with non-angiogenesis inhibitors for the treatment of GC. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched. The extracted data on progression-free survival (PFS) and overall survival (OS) were measured in terms of hazard ratios (HR) and corresponding 95 % confidence intervals (CIs). In addition, risk ratios (RR) and corresponding 95 % CIs were pooled for objective response rate (ORR), disease control rate (DCR), and risk of adverse events (AEs). Ten RCTs involving 2786 patients were included. Compared with non-angiogenesis inhibitor-containing regimens, angiogenesis inhibitor-containing regimens resulted in a significant improvement in OS (HR 0.80, 95 % CI 0.69-0.93, P = 0.004), prolonged PFS (HR 0.66, 95 % CI 0.51-0.86, P = 0.002), and superior ORR (RR 1.34, 95 % CI 1.09-1.65, P = 0.005) and DCR (RR 1.37, 95 % CI 1.17-1.61, P = 0.0001). Angiogenesis inhibitors were associated with a greater number of AEs, but most of these were predictable and manageable. However, hand-foot syndrome, diarrhea, and gastrointestinal (GI) perforation were significantly increased in patients treated with angiogenesis inhibitors. In summary, angiogenesis inhibitor-containing regimens were superior to non-angiogenesis inhibitor-containing regimens in terms of OS, PFS, RR, and DCR in patients with advanced GC.
Topics: Angiogenesis Inhibitors; Disease-Free Survival; Humans; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Rate; Treatment Outcome
PubMed: 27756337
DOI: 10.1186/s13045-016-0340-8 -
Molecules (Basel, Switzerland) Mar 2024The formation of new blood vessels, known as angiogenesis, significantly impacts the development of multiple types of cancer. Consequently, researchers have focused on... (Review)
Review
The formation of new blood vessels, known as angiogenesis, significantly impacts the development of multiple types of cancer. Consequently, researchers have focused on targeting this process to prevent and treat numerous disorders. However, most existing anti-angiogenic treatments rely on synthetic compounds and humanized monoclonal antibodies, often expensive or toxic, restricting patient access to these therapies. Hence, the pursuit of discovering new, affordable, less toxic, and efficient anti-angiogenic compounds is imperative. Numerous studies propose that natural plant-derived products exhibit these sought-after characteristics. The objective of this review is to delve into the anti-angiogenic properties exhibited by naturally derived flavonoids from plants, along with their underlying molecular mechanisms of action. Additionally, we summarize the structure, classification, and the relationship between flavonoids with their signaling pathways in plants as anti-angiogenic agents, including main HIF-1α/VEGF/VEGFR2/PI3K/AKT, Wnt/β-catenin, JNK1/STAT3, and MAPK/AP-1 pathways. Nonetheless, further research and innovative approaches are required to enhance their bioavailability for clinical application.
Topics: Humans; Phosphatidylinositol 3-Kinases; Immunotherapy; Neoplasms; Angiogenesis Inhibitors; Biological Products; Flavonoids
PubMed: 38611849
DOI: 10.3390/molecules29071570 -
Glycobiology Dec 2014Sulfated polysaccharides of brown algae (fucoidans) attract great attention due to their high and strongly diversified biological activity. This review summarizes recent... (Review)
Review
Sulfated polysaccharides of brown algae (fucoidans) attract great attention due to their high and strongly diversified biological activity. This review summarizes recent data on the structural variability of these polysaccharides and reports their anti- and proangiogenic properties. Recent publications have revealed that fucoidans isolated from different algal species may differ considerably in the structures of their backbones and branches, in both monosaccharide composition and sulfate content. It was found that the degree of sulfation significantly influences the biological properties of fucoidans. Additionally, fucoidan action in angiogenesis is highly dependent on molecular weight: antiangiogenic activity is connected with the high-molecular weight of polysaccharide molecules, whereas the low-molecular-weight fractions may act as proangiogenic agents. The influence of other fine structural details of fucoidans on angiogenesis remains to be established.
Topics: Angiogenesis Inhibitors; Carbohydrate Conformation; Humans; Molecular Sequence Data; Molecular Weight; Neovascularization, Physiologic; Polysaccharides
PubMed: 24973252
DOI: 10.1093/glycob/cwu063 -
European Journal of Pharmacology Dec 2016Angiogenesis has become an attractive target for cancer therapy since the US Food and Drug Administration (FDA) approved the first angiogenesis inhibitor (bevacizumab)... (Review)
Review
Angiogenesis has become an attractive target for cancer therapy since the US Food and Drug Administration (FDA) approved the first angiogenesis inhibitor (bevacizumab) for the treatment of metastatic colorectal cancer in 2004. In following years, a large number of angiogenesis inhibitors have been discovered and developed, ranging from monoclonal antibodies, endogenous peptides, to small organic molecules and microRNAs. Many of them are now entering the clinical trial, or achieving approval for clinical use. However, major limitations have been observed about angiogenesis inhibitors by continued clinical investigations, such as resistance, enhancing tumor hypoxia and reducing delivery of chemotherapeutic agents, which might be the main reason for poor improvement in overall survival after angiogenesis inhibitor administration in clinic. Therefore, optimal anti-angiogenic therapy strategies become critical. The present review summarizes recent researches in angiogenesis inhibitors, and proposes a perspective on future directions in this field.
Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Blood Vessels; Humans; Neoplasms
PubMed: 27840192
DOI: 10.1016/j.ejphar.2016.10.039 -
International Journal of Molecular... Dec 2023Angiogenesis significantly influences the carcinogenesis of thymic epithelial tumors (TET). Both thymomas and thymic carcinoma (TC) overexpress VEGF-A and VEGFR-1 and... (Review)
Review
Angiogenesis significantly influences the carcinogenesis of thymic epithelial tumors (TET). Both thymomas and thymic carcinoma (TC) overexpress VEGF-A and VEGFR-1 and -2. This review aims to provide an appraisal of the use of anti-angiogenics in the treatment of TET. The literature research identified 16 studies that were deemed eligible for further analysis. Seven studies assessed the clinical efficacy of sunitinib and five studies the use of apatinib and/or anlotinib. The multicenter Japanese phase II REMORA trial investigated the efficacy of lenvatinib, which is a multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The objective response rate was 38% (25.6-52%), which is the highest documented in TET that progressed after first-line chemotherapy. Anti-angiogenic agents may be useful in the treatment of TET, which are not amenable to curative treatment. Their toxicity profile seems to be acceptable. However, angiogenesis inhibitors do not appear to have a major influence on either thymomas or TC, although multikinase inhibitors may have some effect on TC. The current evidence suggests that the most active agent is lenvatinib, whereas sunitinib could be proposed as an acceptable second-line therapy for TC. Further research concerning the combination of immune checkpoint inhibitors with anti-angiogenic drugs is warranted.
Topics: Humans; Thymoma; Angiogenesis Inhibitors; Sunitinib; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Multicenter Studies as Topic
PubMed: 38069386
DOI: 10.3390/ijms242317065 -
Pharmacology & Therapeutics Oct 2023Vascular anomalies (VA) are developmental anomalies of veins, arteries, lymphatics or capillaries thought to be caused by mutations in genes that drive angiogenesis.... (Review)
Review
Vascular anomalies (VA) are developmental anomalies of veins, arteries, lymphatics or capillaries thought to be caused by mutations in genes that drive angiogenesis. Treatments targeting these genes are limited. We review the literature for conventional medications and products from traditional medicine cultures that have been found to have antiangiogenic activity. Fewer than 50 drugs with credible human activity in VA were identified and include β blockers, monoclonal antibodies, microtubule inhibitors, multi-kinase inhibitors, PIK3CA- and RAS-MAPK pathway inhibitors, and thalidomides. Other drug categories of potential interest are ACE-inhibitors, antifungals, antimalarials, MMP9-inhibitors, and over-the-counter compounds used in Eastern traditional medicine. Low toxicity for some offers the possibility of combined use with known effective agents. In addition to already familiar drugs, others with antiangiogenic capabilities already in use in children or adults may deserve further attention for repurposing for VA.
Topics: Child; Humans; Angiogenesis Inhibitors; Drug Repositioning; Antibodies, Monoclonal
PubMed: 37625520
DOI: 10.1016/j.pharmthera.2023.108520 -
Current Pharmaceutical Design 2021Radiation therapy is a widely employed modality that is used to destroy cancer cells, but it also tends to induce changes in the tumor microenvironment and promote... (Review)
Review
BACKGROUND
Radiation therapy is a widely employed modality that is used to destroy cancer cells, but it also tends to induce changes in the tumor microenvironment and promote angiogenesis. Radiation, when used as a sole means of therapeutic approach to treat cancer, tends to trigger the angiogenic pathways, leading to the upregulation of several angiogenic growth factors such as VEGF, bFGF, PDGF and angiogenin. This uncontrolled angiogenesis leads to certain angiogenic disorders like vascular outgrowth and an increase in tumor progression that can pose a serious threat to patients.
OBJECTIVE
This review emphasizes on various components of the tumor microenvironment, angiogenic growth factors and biological effects of radiation on tumors in provoking the relapse. It also describes the angiogenic mechanisms that trigger the tumor relapse after radiation therapy and how angiogenesis inhibitors can help in overcoming this phenomenon. It gives an overview of various angiogenesis inhibitors in pre-clinical as well as in clinical trials.
CONCLUSION
The review focuses on the beneficial effects of the combinatorial therapeutic approach of anti-angiogenesis therapy and radiation in tumor management.
Topics: Angiogenesis Inhibitors; Humans; Intercellular Signaling Peptides and Proteins; Neoplasms; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 33006535
DOI: 10.2174/1381612826666201002145454