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Current Pharmaceutical Design 2020The role of angiogeneses during the growth and progression of tumors is well documented. Likewise, a balance is generally maintained between the cellular proliferation... (Review)
Review
The role of angiogeneses during the growth and progression of tumors is well documented. Likewise, a balance is generally maintained between the cellular proliferation and the apoptosis, therefore, the tumors can persist for years in a dormant phase. During the past few years, many hypotheses have been proposed relating to the importance of tumor angiogenesis for the development and spread of tumors and preventive or therapeutic capacity of angiogenesis inhibitors as a potential target for controlling the growth of cancerous tissue. The antiangiogenic based therapeutic approaches are considered as the most promising method for the control of tumors, as this therapeutic approach is less likely to attain the drug resistance. Further, the tumor vasculature is an important prognostic marker that can independently predict the pathological stages as well as the metastatic potential of tumors. Various biologically active phytochemicals have been extracted from the dietary sources and the plants that have engaged the scientist and pharmaceutical industries around the globe. The antioxidant, antiinflammatory, anti-proliferative and anti-angiogenic potential of these bioactive phytochemicals is evident from the in vitro studies using cell lines and investigations involving the animal models. The present review is focused on the promising role of anti-angiogenesis-based therapies for the management of tumors and the recent developments relating to the interplay of phytochemicals and angiogenesis for the suppression of tumor cells.
Topics: Angiogenesis Inhibitors; Animals; Humans; Neoplasms; Neovascularization, Pathologic; Phytochemicals
PubMed: 31886747
DOI: 10.2174/1381612826666191230142638 -
Frontiers in Immunology 2023Blood vessels are a key target for cancer therapy. Compared with the healthy vasculature, tumor blood vessels are extremely immature, highly permeable, and deficient in... (Review)
Review
Blood vessels are a key target for cancer therapy. Compared with the healthy vasculature, tumor blood vessels are extremely immature, highly permeable, and deficient in pericytes. The aberrantly vascularized tumor microenvironment is characterized by hypoxia, low pH, high interstitial pressure, and immunosuppression. The efficacy of chemotherapy, radiotherapy, and immunotherapy is affected by abnormal blood vessels. Some anti-angiogenic drugs show vascular normalization effects in addition to targeting angiogenesis. Reversing the abnormal state of blood vessels creates a normal microenvironment, essential for various cancer treatments, specifically immunotherapy. In addition, immune cells and molecules are involved in the regulation of angiogenesis. Therefore, combining vascular normalization with immunotherapy may increase the efficacy of immunotherapy and reduce the risk of adverse reactions. In this review, we discussed the structure, function, and formation of abnormal vessels. In addition, we elaborated on the role of the immunosuppressive microenvironment in the formation of abnormal vessels. Finally, we described the clinical challenges associated with the combination of immunotherapy with vascular normalization, and highlighted future research directions in this therapeutic area.
Topics: Humans; Neoplasms; Immunotherapy; Immunosuppression Therapy; Angiogenesis Inhibitors; Cross Reactions; Tumor Microenvironment
PubMed: 38193080
DOI: 10.3389/fimmu.2023.1291530 -
Angiogenesis Nov 2020Ovarian cancer (OC) is associated with poor survival because there are a limited number of effective therapies. Two processes key to OC progression, angiogenesis and... (Review)
Review
Ovarian cancer (OC) is associated with poor survival because there are a limited number of effective therapies. Two processes key to OC progression, angiogenesis and immune evasion, act synergistically to promote tumor progression. Tumor-associated angiogenesis promotes immune evasion, and tumor-related immune responses in the peritoneal cavity and tumor microenvironment (TME) affect neovascular formation. Therefore, suppressing the angiogenic pathways could facilitate the arrival of immune effector cells and reduce the presence of myeloid cells involved in immune suppression. To date, clinical studies have shown significant benefits with antiangiogenic therapy as first-line therapy in OC, as well as in recurrent disease, and the vascular endothelial growth factor (VEGF) inhibitor bevacizumab is now an established therapy. Clinical data with immunomodulators in OC are more limited, but suggest that they could benefit some patients with recurrent disease. The preliminary results of two phase III trials have shown that the addition of immunomodulators to chemotherapy does not improve progression-free survival. For this reason, it could be interesting to look for synergistic effects between immunomodulators and other active drugs in OC. Since bevacizumab is approved for use in OC, and is tolerable when used in combination with immunotherapy in other indications, a number of clinical studies are underway to investigate the use of bevacizumab in combination with immunotherapeutic agents in OC. This strategy seeks to normalize the TME via the anti-VEGF actions of bevacizumab, while simultaneously stimulating the immune response via the immunotherapy. Results of these studies are awaited with interest.
Topics: Angiogenesis Inhibitors; Combined Modality Therapy; Female; Humans; Immune System; Immunotherapy; Neovascularization, Pathologic; Ovarian Neoplasms
PubMed: 32691290
DOI: 10.1007/s10456-020-09734-w -
Drug Metabolism Reviews Nov 2022Anti-angiogenic therapy is a practical approach to managing diseases with increased angiogenesis, such as cancer, maculopathies, and retinopathies. Considering the... (Review)
Review
Anti-angiogenic therapy is a practical approach to managing diseases with increased angiogenesis, such as cancer, maculopathies, and retinopathies. Considering the fundamental gaps in the knowledge of the vital pathways involved in angiogenesis and its inhibition and the insufficient efficiency of existing angiogenesis inhibitors, there is an increasing focus on the emergence of new therapeutic strategies aimed at inhibiting pathological angiogenesis. Angiogenesis is forming a new vascular network from existing vessels; endothelial cells (ECs), vascular lining cells, are the main actors of angiogenesis in physiological or pathological conditions. Switching from a quiescent state to a highly migratory and proliferative state during new vessel formation called "angiogenic switch" is driven by a "metabolic switch" in ECs, angiogenic growth factors, and other signals. As the characteristics of ECs change by altering the surrounding environment, they appear to have a different metabolism in a tumor microenvironment (TME). Therefore, pathological angiogenesis can be inhibited by targeting metabolic pathways. In the current review, we aim to discuss the EC metabolic pathways under normal and TME conditions to verify the suitability of targeting them with novel therapies.
Topics: Humans; Endothelial Cells; Neovascularization, Pathologic; Neoplasms; Angiogenesis Inhibitors; Intercellular Signaling Peptides and Proteins; Tumor Microenvironment
PubMed: 36031813
DOI: 10.1080/03602532.2022.2116033 -
Cancer Treatment and Research... 2022Vascularization is fundamental to the growth and spread of tumor cells to distant sites. As a consequence, angiogenesis, the sprouting of new blood vessels from existing... (Review)
Review
Vascularization is fundamental to the growth and spread of tumor cells to distant sites. As a consequence, angiogenesis, the sprouting of new blood vessels from existing ones, is a characteristic trait of cancer. In 1971, Judah Folkman postulated that tumour growth is angiogenesis dependent and that by cutting off blood supply, a neoplastic lesion could be potentially starved into remission. Decades of research have been devoted to understanding the role that vascular endothelial growth factor (VEGF) plays in tumor angiogenesis, and it has been identified as a significant pro-angiogenic factor that is frequently overexpressed within a tumor mass. Today, anti-VEGF drugs such as Sunitinib, Sorafenib, Axitinib, Tanibirumab, and Ramucirumab have been approved for the treatment of advanced and metastatic cancers. However, anti-angiogenic therapy has turned out to be more complex than originally thought. The failure of this therapeutic option calls for a reevaluation of VEGF as the major target in anti-angiogenic cancer therapy. The call for reassessment is based on two rationales: first, tumour blood vessels are abnormal, disorganized, and leaky; this not only prevents optimal drug delivery but it also promotes hypoxia and metastasis; secondly, tumour growth or regrowth might be blood vessel dependent and not angiogenesis dependent as tumour cells can acquire blood vessels via non-angiogenic mechanisms. Therefore, a critical assessment of VEGF, VEGFRs, and their inhibitors could glean newer options such as repurposing anti-VEGF drugs as vascular normalizing agents to enhance drug delivery of immune checkpoint inhibitors.
Topics: Angiogenesis Inhibitors; Humans; Neoplasms; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 35964475
DOI: 10.1016/j.ctarc.2022.100620 -
European Journal of Pharmacology May 2021Aspirin is an old drug extracted from willow bark and is widely used for the prevention and treatment of cardiovascular diseases. Accumulating evidence has shown that... (Review)
Review
Aspirin is an old drug extracted from willow bark and is widely used for the prevention and treatment of cardiovascular diseases. Accumulating evidence has shown that aspirin use may significantly reduce the angiogenesis of cancer; however, the mechanism of the association between angiogenesis and aspirin is complex. Although COX-1 is widely known as a target of aspirin, several studies reveal other antiangiogenic targets of aspirin, such as angiotensin II, glucose transporter 1, heparanase, and matrix metalloproteinase. In addition, some data indicates that aspirin may produce antiangiogenic effects after acting in different cell types, such as endothelial cells, platelets, pericytes, and macrophages. In this review, we concentrate on research regarding the antiangiogenic effects of aspirin in cancer, and we discuss the molecular mechanisms of aspirin and its metabolites. Moreover, we discuss some mechanisms through which aspirin treatment may normalize existing blood vessels, including preventing the disintegration of endothelial adheres junctions and the recruitment of pericytes. We also address the antiangiogenic effects and the underlying mechanisms of aspirin derivatives, which are aimed at improving safety and efficacy.
Topics: Angiogenesis Inhibitors; Animals; Aspirin; Humans; Neoplasms; Neovascularization, Pathologic; Signal Transduction
PubMed: 33657423
DOI: 10.1016/j.ejphar.2021.173989 -
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 -
Pathology, Research and Practice Aug 2022Breast cancer is one of the most common cancers in women, which can metastasize to other organs and has a high mortality rate. Previous studies have shown that... (Review)
Review
Breast cancer is one of the most common cancers in women, which can metastasize to other organs and has a high mortality rate. Previous studies have shown that angiogenic factors can contribute to tumor growth, development, and metastasis by altering the tumor microenvironment (TME). These angiogenic factors include a wide range of molecules, and in contrast, anti-angiogenic factors also inhibit angiogenesis and inhibit tumor growth. Evidence suggests that an imbalance between angiogenic and anti-angiogenic factors leads to angiogenesis, facilitating the migration of tumor cells from the source tissue in the breast to other organs such as the lung, liver, bone, and brain. By supplying blood through these neomicrovascular vessels, the nutrients and oxygen needed to grow tumor cells are provided. Due to the significant anti-tumor role of anti-angiogenesis factors, cancer researchers have always considered these molecules, and it is believed that anti-angiogenesis factors can be employed in cancer treatment approaches. This review discusses the role of anti-angiogenesis agents in breast cancer pathogenesis and reviews therapeutic approaches based on anti-angiogenesis factors.
Topics: Angiogenesis Inducing Agents; Angiogenesis Inhibitors; Breast Neoplasms; Female; Humans; Immunotherapy; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 35700578
DOI: 10.1016/j.prp.2022.153956 -
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 -
Molecular Biology Reports Jun 2020Cancer is a major problem in the health system, and despite many efforts to effectively treat it, none has yet been fully successful. Angiogenesis and metastasis are... (Review)
Review
Cancer is a major problem in the health system, and despite many efforts to effectively treat it, none has yet been fully successful. Angiogenesis and metastasis are considered as major challenges in the treatment of various cancers. Researchers have struggled to succeed with anti-angiogenesis drugs for the effective treatment of cancer, although new challenges have emerged in the treatment with the emergence of resistance to anti-angiogenesis and anti-metastatic drugs. Numerous studies have shown that different cancers can resist anti-angiogenesis drugs in a new process called vascular mimicry (VM). The studies have revealed that cells resistant to anti-angiogenesis cancer therapies are more capable of forming VMs in the in vivo and in vitro environment, although there is a link between the presence of VM and poor clinical outcomes. Given the importance of the VM in the challenges facing cancer treatment, researchers are trying to identify factors that prevent the formation of these structures. In this review article, it is attempted to provide a comprehensive overview of the molecules and main signaling pathways involved in VM phenomena, as well as the agents currently being identified as anti-VM and the role of VM in response to treatment and prognosis of cancer patients.
Topics: Angiogenesis Inhibitors; Antigens, CD; Cadherins; Humans; Neoplasms; Neovascularization, Pathologic; Prognosis; Signal Transduction
PubMed: 32424524
DOI: 10.1007/s11033-020-05515-2