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Oncogenesis Jun 2015Since the establishment of tumor angiogenesis as a therapeutic target, an excitement in developing the anti-angiogenic agents was resulted in tailoring a humanized... (Review)
Review
Since the establishment of tumor angiogenesis as a therapeutic target, an excitement in developing the anti-angiogenic agents was resulted in tailoring a humanized monoclonal antibody (Bevacizumab) against vascular endothelial growth factor (VEGF): a key factor in recruiting angiogenesis. The past three decades' research in the area of angiogenesis also invented a series of novel and effective anti-angiogenic agents targeting the VEGF signaling axis. Despite the demonstrable clinical benefits of anti-angiogenic therapy, the preclinical and clinical data of the current therapeutic settings clearly indicate the transient efficacy, restoration of tumor progression and aggressive recurrence of tumor invasion after the withdrawal of anti-angiogenic therapy. Therefore, the impact of this therapeutic regime on improving overall survival of patients has been disappointing in clinic. The recent advances in pathophysiology of tumor angiogenesis and related molecular and cellular underpinnings attributed the conspiracy of compensatory angiogenic pathways in conferring evasive and intrinsic tumor resistance to anti-angiogenic agents. The understandings of how these pathways functionally cross-talk for sustaining tumor angiogenesis during VEGF blockade is essential and perhaps may act as a basic prerequisite for designing novel therapeutic strategies to combat the growing arrogance of tumors toward anti-angiogenic agents. The present review offers a discourse on major compensatory angiogenic pathways operating at cellular and molecular levels and their attributes with resistance to anti-angiogenic agents along with strategic opinions on future setting in targeting tumor angiogenesis.
PubMed: 26029827
DOI: 10.1038/oncsis.2015.14 -
Frontiers in Oncology 2021Breast cancer is the most common cancer affecting women and is the second leading cause of cancer related death worldwide. Angiogenesis, the process of new blood vessel... (Review)
Review
Breast cancer is the most common cancer affecting women and is the second leading cause of cancer related death worldwide. Angiogenesis, the process of new blood vessel development from pre-existing vasculature, has been implicated in the growth, progression, and metastasis of cancer. Tumor angiogenesis has been explored as a key therapeutic target for decades, as the blockade of this process holds the potential to reduce the oxygen and nutrient supplies that are required for tumor growth. However, many existing anti-angiogenic approaches, such as those targeting Vascular Endothelial Growth Factor, Notch, and Angiopoietin signaling, have been associated with severe side-effects, limited survival advantage, and enhanced cancer regrowth rates. To address these setbacks, alternative pathways involved in the regulation of tumor angiogenesis are being explored, including those involving Bone Morphogenetic Protein-9 signaling, the Sonic Hedgehog pathway, Cyclooxygenase-2, p38-mitogen-activated protein kinase, and Chemokine Ligand 18. This review article will introduce the concept of tumor angiogenesis in the context of breast cancer, followed by an overview of current anti-angiogenic therapies, associated resistance mechanisms and novel therapeutic targets.
PubMed: 34926282
DOI: 10.3389/fonc.2021.772305 -
Biomedicine & Pharmacotherapy =... Jul 2018Glycosylation is an enzymatic process in which a carbohydrate is attached to a functional group from another molecule. Glycosylation is a crucial post translational... (Review)
Review
Glycosylation is an enzymatic process in which a carbohydrate is attached to a functional group from another molecule. Glycosylation is a crucial post translational process in protein modification. The tumor microenvironment produces altered glycans that contribute to cancer progression and aggressiveness. Abnormal glycosylation is widely observed in tumor angiogenesis. Despite many attempts to decipher the role of glycosylation in different aspects of cancer, little is known regarding the roles of glycans in angiogenesis. The blood vessels in tumors are often used to transport oxygen and nutrients for tumor progression and metastasis. The crosstalk within the tumor microenvironment can induce angiogenesis by manipulating these glycans to hijack the normal angiogenesis process, thus promoting tumor growth. Abnormal glycosylation has been shown to promote tumor angiogenesis by degrading the extracellular matrix to activate the angiogenic signaling pathways. This review highlights the latest update on how glycosylation can contribute to tumor angiogenesis that may affect treatment outcomes.
Topics: Animals; Glycosylation; Humans; Models, Biological; Neoplasms; Neovascularization, Pathologic
PubMed: 29864905
DOI: 10.1016/j.biopha.2018.04.119 -
Cancer Microenvironment : Official... Jun 2018The development of cancer involves an intricate process, wherein many identified and unidentified factors play a role. Tumor angiogenesis, growth of new blood vessels,... (Review)
Review
The development of cancer involves an intricate process, wherein many identified and unidentified factors play a role. Tumor angiogenesis, growth of new blood vessels, is one of the major prerequisites for tumor growth as tumor cells rely on adequate oxygen and nutrient supply as well as the removal of waste products. Growth factors including VEGF orchestrate the development of angiogenesis. In addition, nervous system via the release of neurotransmitters contributes to tumor angiogenesis. The nervous system governs functional activities of many organs, and, as tumors are not independent organs within an organism, this system is integrally involved in tumor growth and progression via regulating tumor angiogenesis. Various neurotransmitters have been reported to play an important role in tumor angiogenesis.
PubMed: 29502307
DOI: 10.1007/s12307-018-0207-3 -
Frontiers in Oncology 2021Tumor-associated angiogenesis is a key target for anti-cancer therapy. The imbalance between pro-angiogenic and anti-angiogenic signals elicited by tumor cells or tumor... (Review)
Review
Tumor-associated angiogenesis is a key target for anti-cancer therapy. The imbalance between pro-angiogenic and anti-angiogenic signals elicited by tumor cells or tumor microenvironment always results in activating "angiogenic switch". Tumor angiogenesis functions in multi-aspects of tumor biology, including endothelial cell apoptosis, tumor metastasis, and cancer stem cell proliferation. Numerous studies have indicated the important roles of inexpensive and less toxic natural products in targeting tumor angiogenesis-associated cytokines and apoptotic signaling pathways. Our current knowledge of tumor angiogenesis is based mainly on experiments performed on cells and animals, so we summarized the well-established models for angiogenesis both and . In this review, we classified and summarized the anti-angiogenic natural agents (Polyphenols, Polysaccharides, Alkaloids, Terpenoids, Saponins) in targeting various tumor types according to their chemical structures at present, and discussed the mechanistic principles of these natural products on regulating angiogenesis-associated cytokines and apoptotic signaling pathways. This review is to help understanding the recent progress of natural product research for drug development on anti-tumor angiogenesis.
PubMed: 34746014
DOI: 10.3389/fonc.2021.772915 -
Acta Neuropathologica Dec 2012The cellular and molecular mechanisms of tumor angiogenesis and its prospects for anti-angiogenic cancer therapy are major issues in almost all current concepts of both... (Review)
Review
The cellular and molecular mechanisms of tumor angiogenesis and its prospects for anti-angiogenic cancer therapy are major issues in almost all current concepts of both cancer biology and targeted cancer therapy. Currently, (1) sprouting angiogenesis, (2) vascular co-option, (3) vascular intussusception, (4) vasculogenic mimicry, (5) bone marrow-derived vasculogenesis, (6) cancer stem-like cell-derived vasculogenesis and (7) myeloid cell-driven angiogenesis are all considered to contribute to tumor angiogenesis. Many of these processes have been described in developmental angiogenesis; however, the relative contribution and relevance of these in human brain cancer remain unclear. Preclinical tumor models support a role for sprouting angiogenesis, vascular co-option and myeloid cell-derived angiogenesis in glioma vascularization, whereas a role for the other four mechanisms remains controversial and rather enigmatic. The anti-angiogenesis drug Avastin (Bevacizumab), which targets VEGF, has become one of the most popular cancer drugs in the world. Anti-angiogenic therapy may lead to vascular normalization and as such facilitate conventional cytotoxic chemotherapy. However, preclinical and clinical studies suggest that anti-VEGF therapy using bevacizumab may also lead to a pro-migratory phenotype in therapy resistant glioblastomas and thus actively promote tumor invasion and recurrent tumor growth. This review focusses on (1) mechanisms of tumor angiogenesis in human malignant glioma that are of particular relevance for targeted therapy and (2) controversial issues in tumor angiogenesis such as cancer stem-like cell-derived vasculogenesis and bone-marrow-derived vasculogenesis.
Topics: Angiogenesis Inhibitors; Brain Neoplasms; Glioma; Humans; Neovascularization, Pathologic; Signal Transduction
PubMed: 23143192
DOI: 10.1007/s00401-012-1066-5 -
Journal of Cellular and Molecular... Mar 2021Angiogenesis plays an important role in tumour progression. However, anti-angiogenesis therapy of inhibiting pro-angiogenic factors failed to meet expectations in... (Review)
Review
Angiogenesis plays an important role in tumour progression. However, anti-angiogenesis therapy of inhibiting pro-angiogenic factors failed to meet expectations in certain types of tumour in clinical trials. Recent studies reveal that tumour-derived extracellular vesicles (EVs) are essential in tumour angiogenesis and anti-angiogenesis drug resistance. This function has most commonly been attributed to EV contents including proteins and non-coding RNAs. Here, we summarize the recent findings of tumour-derived EV contents associated with regulating angiogenesis and illustrate the underlying mechanisms. In addition, the roles of EVs in tumour microenvironmental cells are also illustrated with a focus on how EVs participate in cell-cell communication, contributing to tumour-mediated angiogenesis. It will help offer new perspectives on developing targets of anti-angiogenesis drugs and improve the efficacy of anti-angiogenesis therapies based on tumour-derived EVs.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Biomarkers; Drug Resistance, Neoplasm; Extracellular Vesicles; Humans; Molecular Targeted Therapy; Neoplasms; Neoplastic Stem Cells; Neovascularization, Pathologic; RNA, Untranslated; Tumor Microenvironment
PubMed: 33586248
DOI: 10.1111/jcmm.16359 -
Methods in Molecular Biology (Clifton,... 2013The evaluation of tumor angiogenesis in pancreatic cancers involves determining the status of tumor vasculature and hypoxia in the tumor. Describing the nature and...
The evaluation of tumor angiogenesis in pancreatic cancers involves determining the status of tumor vasculature and hypoxia in the tumor. Describing the nature and extent of tumor angiogenesis involves evaluating the expression of endothelial and perivascular cells within the tumor, and the expression of angiogenesis-related genes in tumor vasculature. Here we describe the methodology for assessment of tumor vasculature in murine mouse models of cancer. Specifically, we provide methodology for the evaluation of tumor hypoxia, tumor vessel perfusion, and chromogenic and fluorescent immunohistochemistry applied to tumor vascular analysis.
Topics: Animals; Disease Models, Animal; Humans; Hypoxia; Immunohistochemistry; Mice; Neoplasms; Neovascularization, Pathologic; Pancreatic Neoplasms
PubMed: 23359165
DOI: 10.1007/978-1-62703-287-2_20 -
Cells Mar 2022Extracellular vesicles (EVs) act as multifunctional regulators of intercellular communication and are involved in diverse tumor phenotypes, including tumor angiogenesis,... (Review)
Review
Extracellular vesicles (EVs) act as multifunctional regulators of intercellular communication and are involved in diverse tumor phenotypes, including tumor angiogenesis, which is a highly regulated multi-step process for the formation of new blood vessels that contribute to tumor proliferation. EVs induce malignant transformation of distinct cells by transferring DNAs, proteins, lipids, and RNAs, including noncoding RNAs (ncRNAs). However, the functional relevance of EV-derived ncRNAs in tumor angiogenesis remains to be elucidated. In this review, we summarized current research progress on the biological functions and underlying mechanisms of EV-derived ncRNAs in tumor angiogenesis in various cancers. In addition, we comprehensively discussed the potential applications of EV-derived ncRNAs as cancer biomarkers and novel therapeutic targets to tailor anti-angiogenic therapy.
Topics: Biomarkers, Tumor; Extracellular Vesicles; Humans; Neoplasms; Neovascularization, Pathologic; RNA, Untranslated
PubMed: 35326397
DOI: 10.3390/cells11060947 -
Biochimica Et Biophysica Acta. Reviews... Apr 2020Redox reactions pervade all biology. The control of cellular redox state is essential for bioenergetics and for the proper functioning of many biological functions. This... (Review)
Review
Redox reactions pervade all biology. The control of cellular redox state is essential for bioenergetics and for the proper functioning of many biological functions. This review traces a timeline of findings regarding the connections between redox and cancer. There is ample evidence of the involvement of cellular redox state on the different hallmarks of cancer. Evidence of the control of tumor angiogenesis and metastasis through modulation of cell redox state is reviewed and highlighted.
Topics: Disease Progression; Humans; Neoplasms; Neovascularization, Pathologic; Oxidation-Reduction; Signal Transduction
PubMed: 32035101
DOI: 10.1016/j.bbcan.2020.188352