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Oncology Letters Jul 2018When Folkman first suggested a theory about the association between angiogenesis and tumor growth in 1971, the hypothesis of targeting angiogenesis to treat cancer was... (Review)
Review
When Folkman first suggested a theory about the association between angiogenesis and tumor growth in 1971, the hypothesis of targeting angiogenesis to treat cancer was formed. Since then, various studies conducted across the world have additionally confirmed the theory of Folkman, and numerous efforts have been made to explore the possibilities of curing cancer by targeting angiogenesis. Among them, anti-angiogenic gene therapy has received attention due to its apparent advantages. Although specific problems remain prior to cancer being fully curable using anti-angiogenic gene therapy, several methods have been explored, and progress has been made in pre-clinical and clinical settings over previous decades. The present review aimed to provide up-to-date information concerning tumor angiogenesis and gene delivery systems in anti-angiogenic gene therapy, with a focus on recent developments in the study and application of the most commonly studied and newly identified anti-angiogenic candidates for anti-angiogenesis gene therapy, including interleukin-12, angiostatin, endostatin, tumstatin, anti-angiogenic metargidin peptide and endoglin silencing.
PubMed: 29963134
DOI: 10.3892/ol.2018.8733 -
Journal of Cancer Research and Clinical... Dec 2021The development of blood vessels, referred to as angiogenesis, is an intricate process regulated spatially and temporally through a delicate balance between the... (Review)
Review
The development of blood vessels, referred to as angiogenesis, is an intricate process regulated spatially and temporally through a delicate balance between the qualitative and quantitative expression of pro and anti-angiogenic molecules. As angiogenesis is a prerequisite for solid tumors to grow and metastasize, a variety of tumor angiogenesis models have been formulated to better understand the underlying mechanisms and associated clinical applications. Studies have demonstrated independent mechanisms inducing angiogenesis in tumors such as (a) HIF-1/VEGF mediated paracrine interactions between a cancer cell and endothelial cells, (b) recruitment of progenitor endothelial cells, and (c) vasculogenic mimicry. Moreover, single-cell sequencing technologies have indicated endothelial cell heterogeneity among organ systems including tumor tissues. However, existing angiogenesis models often rely upon normal endothelial cells which significantly differ from tumor endothelial cells exhibiting distinct (epi)genetic and metabolic signatures. Besides, the existence of intra-individual variations necessitates the development of improved tumor vascular model systems for personalized medicine. In the present review, we summarize recent advancements of 3D tumor vascular model systems which include (a) tissue engineering-based tumor models; (b) vascular organoid models, and (c) organ-on-chips and their importance in replicating the tumor angiogenesis along with the associated challenges to design improved models.
Topics: Animals; Humans; Neoplasms; Neovascularization, Pathologic; Organoids; Tissue Engineering
PubMed: 34613483
DOI: 10.1007/s00432-021-03814-0 -
Experimental Cell Research Jan 2019Erythropoietin (EPO) is a moonlighting protein since is ability to work as hormone, cytokine and growth factor. Its cardinal function is to regulate erythropoiesis in... (Review)
Review
Erythropoietin (EPO) is a moonlighting protein since is ability to work as hormone, cytokine and growth factor. Its cardinal function is to regulate erythropoiesis in the bone marrow. However, EPO with his receptor EPOR are expressed also in non-hematopoietic tissues such as endothelium where they exert a protective function. Moreover, it is known EPO-EPOR pathway contribute to neovascularization in the angiogenic switch of tumor, but the mechanism is not completely established. In this article, after a brief introduction on tumor angiogenesis and description of classical and non-classical pro-angiogenic factors, we review the role of EPO in tumor angiogenesis highlighting the different mechanisms activated by it to promote tumor growth and progression. Finally, we analyze the controversy between the beneficial and the harmful effects of EPO. We suppose that the accurate characterization of EPO variants and their downstream pathways will allow to develop specific inhibition strategies to block only EPOR expressed by tumor cells without inducing signalling in hematopoietic cells to avoid side effects.
Topics: Animals; Cell Proliferation; Erythropoietin; Humans; Neoplasms; Neovascularization, Pathologic; Signal Transduction
PubMed: 30576679
DOI: 10.1016/j.yexcr.2018.12.013 -
The Journal of Investigative... Dec 2000In order to grow beyond minimal size and to metastasize, tumors need to induce the growth of new blood vessels (angiogenesis). Whereas in normal tissues, vascular... (Review)
Review
In order to grow beyond minimal size and to metastasize, tumors need to induce the growth of new blood vessels (angiogenesis). Whereas in normal tissues, vascular quiescence is maintained by the dominant influence of endogenous angiogenesis inhibitors over angiogenic stimuli, tumor angiogenesis is induced by increased secretion of angiogenic factors and/or by downregulation of angiogenesis inhibitors. Recent evidence suggests vascular endothelial growth factor (VEGF) as the major tumor angiogenesis factor, promoting tumor growth, invasion, and metastasis. Conversely, blocking of VEGF function inhibits angiogenesis and suppresses tumor growth in vivo. Newly identified members of the VEGF family of angiogenesis factors include placental growth factor, VEGF-B, VEGF-C, and VEGF-D, and show overlapping binding patterns to specific endothelial cell receptors. VEGF-C appears to play a major role as a lymphangiogenesis factor and as a growth factor for Kaposi's sarcoma. In contrast, endogenous inhibitors prevent blood vessel growth in normal tissues. In particular, thrombospondin-1 (TSP-1) and TSP-2 are expressed in normal skin and, when introduced into squamous cell carcinomas, potently inhibit malignant tumor growth via inhibition of tumor angiogenesis.
Topics: Animals; Endothelial Growth Factors; Humans; Lymphokines; Neovascularization, Pathologic; Skin Neoplasms; Thrombospondin 1; Thrombospondins; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 11147670
DOI: 10.1046/j.1087-0024.2000.00003.x -
Frontiers in Pharmacology 2022Tumor angiogenesis is one of the most important processes of cancer deterioration nurturing an immunosuppressive tumor environment (TME). Targeting tumor angiogenesis... (Review)
Review
Tumor angiogenesis is one of the most important processes of cancer deterioration nurturing an immunosuppressive tumor environment (TME). Targeting tumor angiogenesis has been widely accepted as a cancer intervention approach, which is also synergistically associated with immune therapy. However, drug resistance is the biggest challenge of anti-angiogenesis therapy, which affects the outcomes of anti-angiogeneic agents, and even combined with immunotherapy. Here, emerging targets and representative candidate molecules from ethnopharmacology (including traditional Chinese medicine, TCM) have been focused, and they have been proved to regulate tumor angiogenesis. Further investigations on derivatives and delivery systems of these molecules will provide a comprehensive landscape in preclinical studies. More importantly, the molecule library of ethnopharmacology meets the viability for targeting angiogenesis and TME simultaneously, which is attributed to the pleiotropy of pro-angiogenic factors (such as VEGF) toward cancer cells, endothelial cells, and immune cells. We primarily shed light on the potentiality of ethnopharmacology against tumor angiogenesis, particularly TCM. More research studies concerning the crosstalk between angiogenesis and TME remodeling from the perspective of botanical medicine are awaited.
PubMed: 35784750
DOI: 10.3389/fphar.2022.886198 -
Cancer Science Jul 2023Tumor angiogenesis plays an important role in the development of cancer as it allows the delivery of oxygen, nutrients, and growth factors as well as tumor dissemination... (Review)
Review
Tumor angiogenesis plays an important role in the development of cancer as it allows the delivery of oxygen, nutrients, and growth factors as well as tumor dissemination to distant organs. Although anti-angiogenic therapy (AAT) has been approved for treating various advanced cancers, this potential strategy has limited efficacy due to resistance over time. Therefore, there is a critical need to understand how resistance develops. Extracellular vesicles (EVs) are nano-sized membrane-bound phospholipid vesicles produced by cells. A growing body of evidence suggests that tumor cell-derived EVs (T-EVs) directly transfer their cargoes to endothelial cells (ECs) to promote tumor angiogenesis. Importantly, recent studies have reported that T-EVs may play a major role in the development of resistance to AAT. Moreover, studies have demonstrated the role of EVs from non-tumor cells in angiogenesis, although the mechanisms involved are still not completely understood. In this review, we provide a comprehensive description of the role of EVs derived from various cells, including tumor cells and non-tumor cells, in tumor angiogenesis. Moreover, from the perspective of EVs, this review summarized the role of EVs in the resistance to AAT and the mechanisms involved. Due to their role in the resistance of AAT, we here proposed potential strategies to further improve the efficacy of AAT by inhibiting T-EVs.
Topics: Humans; Endothelial Cells; Neovascularization, Pathologic; Extracellular Vesicles; Cell Communication
PubMed: 37010195
DOI: 10.1111/cas.15801 -
Journal of Controlled Release :... Aug 2023Tumor angiogenesis and cancer stem cells (CSCs) are two major hallmarks of solid tumors. They have long received attention for their critical roles in tumor progression,... (Review)
Review
Tumor angiogenesis and cancer stem cells (CSCs) are two major hallmarks of solid tumors. They have long received attention for their critical roles in tumor progression, metastasis and recurrence. Meanwhile, plenty of evidence indicates the close association between CSCs and tumor vasculature. CSCs are proven to promote tumor angiogenesis, and the highly vascularized tumor microenvironment further maintains CSCs growth in return, thereby forming a hard-breaking vicious circle to promote tumor development. Hence, though monotherapy targeting tumor vasculature or CSCs has been extensively studied over the past decades, the poor prognosis has been limiting the clinical application. This review summarizes the crosstalk between tumor vasculature and CSCs with emphasis on small-molecule compounds and the associated biological signaling pathways. We also highlight the importance of linking tumor vessels to CSCs to disrupt the CSCs-angiogenesis vicious circle. More precise treatment regimens targeting tumor vasculature and CSCs are expected to benefit future tumor treatment development.
Topics: Humans; Neoplasms; Neovascularization, Pathologic; Neoplastic Stem Cells; Tumor Microenvironment
PubMed: 37391031
DOI: 10.1016/j.jconrel.2023.06.036 -
Frontiers in Cell and Developmental... 2021Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins, but perform biological functions in various physiological and pathological processes, including cancer... (Review)
Review
Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins, but perform biological functions in various physiological and pathological processes, including cancer formation, inflammation, and neurological diseases. Tumor blood vessels are a key target for cancer management. A number of factors regulate the angiogenesis of malignant tumors. NcRNAs participate in the regulation of tumor angiogenesis. Abnormal expression of ncRNAs act as tumor suppressors or oncogenes to affect the development of tumors. In this review we summarized the biological functions of ncRNAs, and discussed its regulatory mechanisms in tumor angiogenesis. This article will provide new insights for the research of ncRNAs in tumor angiogenesis.
PubMed: 34616746
DOI: 10.3389/fcell.2021.751578 -
Journal of the Medical Association of... Apr 1999Tumor angiogenesis is the growth of new blood vessels which is required for tumor growth and progression. Vascularization of the tumor occurs through a series of... (Review)
Review
Tumor angiogenesis is the growth of new blood vessels which is required for tumor growth and progression. Vascularization of the tumor occurs through a series of sequential steps before or during the multistep progression to neoplasia. Several events occur during the formation of new vessels including production of protease enzymes, unregulation of positive regulators of angiogenesis, and down regulation of negative regulators. In addition, tumor associated macrophage also influence angiogenesis by secreting enzymes, enzymes inhibitors and cytokines. Recent knowledge in tumor angiogenesis may have clinical implications in diagnosis and treatment. Quantification of microvessel density in tumor specimen correlates either metastasis or recurrence in many malignancies such as breast cancer and lung cancer. Therefore, assessment of tumor angiogenesis may serve as prognostic factors. Therapeutic applications include the development of new agents with antiangiogenic properties, vascular targeting drugs, antibody-based therapy, and gene therapy. Combination of antiangiogenic therapy with cytotoxic drugs may enhance antitumor activity. Moreover, the role of antiangiogenic therapy in adjuvant setting may provide and alternative approach to better cancer treatment in the near future.
Topics: Humans; Neoplasms; Neovascularization, Pathologic
PubMed: 10410503
DOI: No ID Found -
International Journal of Molecular... Jun 2022Angiogenesis is involved in physiological and pathological processes in the body. Tumor angiogenesis is a key factor associated with tumor growth, progression, and... (Review)
Review
Angiogenesis is involved in physiological and pathological processes in the body. Tumor angiogenesis is a key factor associated with tumor growth, progression, and metastasis. Therefore, there is great interest in developing antiangiogenic strategies. Hypoxia is the basic initiating factor of tumor angiogenesis, which leads to the increase of vascular endothelial growth factor (VEGF), angiopoietin (Ang), hypoxia-inducible factor (HIF-1), etc. in hypoxic cells. The pathways of VEGF and Ang are considered to be critical steps in tumor angiogenesis. A number of antiangiogenic drugs targeting VEGF/VEGFR (VEGF receptor) or ANG/Tie2, or both, are currently being used for cancer treatment, or are still in various stages of clinical development or preclinical evaluation. This article aims to review the mechanisms of angiogenesis and tumor angiogenesis and to focus on new drugs and strategies for the treatment of antiangiogenesis. However, antitumor angiogenic drugs alone may not be sufficient to eradicate tumors. The molecular chaperone heat shock protein 90 (HSP90) is considered a promising molecular target. The VEGFR system and its downstream signaling molecules depend on the function of HSP90. This article also briefly introduces the role of HSP90 in angiogenesis and some HSP90 inhibitors.
Topics: Angiogenesis Inhibitors; Angiopoietins; Antineoplastic Agents; HSP90 Heat-Shock Proteins; Humans; Hypoxia; Neoplasms; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 35805939
DOI: 10.3390/ijms23136934