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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Targeting VEGF pathway to normalize the vasculature: an emerging insight in cancer therapy

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          Abstract

          Vascular normalization is a new concept of targeting angiogenesis to restore vessel structure and function and to increase blood perfusion and delivery of drugs. It has been confirmed that vascular normalization can decrease relapse and benefit other cancer therapy, including chemotherapy, radiotherapy, and immune cell therapy. The key point of this therapy is to inhibit pro-angiogenic factors and make it be balanced with anti-angiogenic factors, resulting in a mature and normal vessel characteristic. Vascular endothelial growth factor (VEGF) is a key player in the process of tumor angiogenesis, and inhibiting VEGF is a primary approach to tumor vessel normalization. Herein, we review newly uncovered mechanisms governing angiogenesis and vascular normalization of cancer and place emphasis on targeting VEGF pathway to normalize the vasculature. Also, important methods to depress VEGF pathway and make tumor vascular are discussed.

          Most cited references74

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          Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells.

          Although immune mechanisms can suppress tumour growth, tumours establish potent, overlapping mechanisms that mediate immune evasion. Emerging evidence suggests a link between angiogenesis and the tolerance of tumours to immune mechanisms. Hypoxia, a condition that is known to drive angiogenesis in tumours, results in the release of damage-associated pattern molecules, which can trigger the rejection of tumours by the immune system. Thus, the counter-activation of tolerance mechanisms at the site of tumour hypoxia would be a crucial condition for maintaining the immunological escape of tumours. However, a direct link between tumour hypoxia and tolerance through the recruitment of regulatory cells has not been established. We proposed that tumour hypoxia induces the expression of chemotactic factors that promote tolerance. Here we show that tumour hypoxia promotes the recruitment of regulatory T (T(reg)) cells through induction of expression of the chemokine CC-chemokine ligand 28 (CCL28), which, in turn, promotes tumour tolerance and angiogenesis. Thus, peripheral immune tolerance and angiogenesis programs are closely connected and cooperate to sustain tumour growth. ©2011 Macmillan Publishers Limited. All rights reserved
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            miR-126 regulates angiogenic signaling and vascular integrity.

            Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-beta). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function.
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              Angiogenesis: an organizing principle for drug discovery?

              Angiogenesis--the process of new blood-vessel growth--has an essential role in development, reproduction and repair. However, pathological angiogenesis occurs not only in tumour formation, but also in a range of non-neoplastic diseases that could be classed together as 'angiogenesis-dependent diseases'. By viewing the process of angiogenesis as an 'organizing principle' in biology, intriguing insights into the molecular mechanisms of seemingly unrelated phenomena might be gained. This has important consequences for the clinical use of angiogenesis inhibitors and for drug discovery, not only for optimizing the treatment of cancer, but possibly also for developing therapeutic approaches for various diseases that are otherwise unrelated to each other.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2018
                17 October 2018
                : 11
                : 6901-6909
                Affiliations
                State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan, People’s Republic of China, lxh88866@ 123456scu.edu.cn ; tangyaling@ 123456scu.edu.cn
                Author notes
                Correspondence: Xin-hua Liang; Ya-ling Tang, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology (Sichuan University), No 14, Sec. 3, Renminnan Road, Chengdu Sichuan 610041, People’s Republic of China, Tel +86 1 588 448 3965; +86 1 500 845 8098, Email lxh88866@ 123456scu.edu.cn ; tangyaling@ 123456scu.edu.cn
                Article
                ott-11-6901
                10.2147/OTT.S172042
                6200071
                30410348
                c772b5ca-af56-4420-9d41-8ab450ef9e45
                © 2018 Wu et al, publisher and licensee Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed

                History
                Categories
                Review

                Oncology & Radiotherapy
                vascular normalization,vascular endothelial growth factor,anti-angiogenesis,treatment resistance,cancer therapy

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