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      The Impact of Angiogenesis in the Most Common Salivary Gland Malignant Tumors

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          Abstract

          Salivary gland carcinomas (SGCs) represent a group of rare tumors, with complete surgical resection being the main treatment option. Therapeutic armory for cases of locally aggressive, recurrent, and/or metastatic SGCs, though, remains poor since they exhibit high rates of resistance to systematic therapy. Angiogenesis is considered one of the contemporary hallmarks of cancer and anti-angiogenic factors have already been approved for the treatment of several cancer types. This review aims to summarize, in a histotype-specific manner, the most current available data on the angiogenic factors implicated in SGC angiogenesis, in order to highlight the differences between the most common SGC histotypes and the factors that may have a potential role as therapeutic targets.

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          VEGF in Signaling and Disease: Beyond Discovery and Development

          Rajendra Apte, Daniel S. Chen, Napoleone Ferrara (2019)
          The discovery of vascular endothelial-derived growth factor (VEGF) has revolutionized our understanding of vasculogenesis and angiogenesis during development and physiological homeostasis. Over a short span of two decades, our understanding of the molecular mechanisms by which VEGF coordinates neurovascular homeostasis has become more sophisticated. The central role of VEGF in the pathogenesis of diverse cancers and blinding eye diseases has also become evident. Elucidation of the molecular regulation of VEGF and the transformative development of multiple therapeutic pathways targeting VEGF directly or indirectly is a powerful case study of how fundamental research can guide innovation and translation. It is also an elegant example of how agnostic discovery and can transform our understanding of human disease. This review will highlight critical nodal points in VEGF biology including recent developments in immunotherapy for cancer and multi-target approaches in neovascular eye disease.
          Article 0 comments Cited 826 times – based on 0 reviews     Review now
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            Revisiting the hallmarks of cancer.

            Yousef Fouad, Carmen M Aanei (2017)
            The hallmarks of cancer described by Hanahan and Weinberg have proved seminal in our understanding of cancer's common traits and in rational drug design. Not free of critique and with understanding of different aspects of tumorigenesis coming into clearer focus in the recent years, we attempt to draw a more organized and updated picture of the cancer hallmarks. We define seven hallmarks of cancer: selective growth and proliferative advantage, altered stress response favoring overall survival, vascularization, invasion and metastasis, metabolic rewiring, an abetting microenvironment, and immune modulation, while highlighting some considerations for the future of the field.
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              Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?

              Rakesh R Ramjiawan, Arjan Griffioen, Dan G Duda (2017)
              Angiogenesis is defined as the formation of new blood vessels from preexisting vessels and has been characterized as an essential process for tumor cell proliferation and viability. This has led to the development of pharmacological agents for anti-angiogenesis to disrupt the vascular supply and starve tumor of nutrients and oxygen, primarily through blockade of VEGF/VEGFR signaling. This effort has resulted in 11 anti-VEGF drugs approved for certain advanced cancers, alone or in combination with chemotherapy or other targeted therapies. But this success had only limited impact on overall survival of cancer patients and rarely resulted in durable responses. Given the recent success of immunotherapies, combinations of anti-angiogenics with immune checkpoint blockers have become an attractive strategy. However, implementing such combinations will require a better mechanistic understanding of their interaction. Due to overexpression of pro-angiogenic factors in tumors, their vasculature is often tortuous and disorganized, with excessively branched leaky vessels. This enhances vascular permeability, which in turn is associated with high interstitial fluid pressure, and a reduction in blood perfusion and oxygenation. Judicious dosing of anti-angiogenic treatment can transiently normalize the tumor vasculature by decreasing vascular permeability and improving tumor perfusion and blood flow, and synergize with immunotherapy in this time window. However, anti-angiogenics may also excessively prune tumor vessels in a dose and time-dependent manner, which induces hypoxia and immunosuppression, including increased expression of the immune checkpoint programmed death receptor ligand (PD-L1). This review focuses on revisiting the concept of anti-angiogenesis in combination with immunotherapy as a strategy for cancer treatment.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 08 December 2020
                Publication date Collection: December 2020
                Volume: 21
                Issue: 24
                Electronic Location Identifier: 9335
                Affiliations
                [1 ]First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; d.v.pouloudi@ 123456gmail.com (D.P.); ari.sotiriadis@ 123456gmail.com (A.S.); mtheodorakidou@ 123456gmail.com (M.T.); alexperg@ 123456yahoo.com (A.P.)
                [2 ]Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; psarantis@ 123456med.uoa.gr (P.S.); mkaramouz@ 123456med.uoa.gr (M.V.K.)
                Author notes
                [* ]Correspondence: stamtheo@ 123456med.uoa.gr or statheocharis@ 123456yahoo.com ; Tel.: +30-210-7462178; Fax: +30-210-7456259
                [†]

                Equal contribution.

                Author information
                https://orcid.org/0000-0003-1369-8201
                Article
                Publisher ID: ijms-21-09335
                DOI: 10.3390/ijms21249335
                PMC ID: 7762607
                PubMed ID: 33302367
                SO-VID: c2e2fb3c-fadd-461a-9b3e-7e589ecd3695
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 02 November 2020
                Date accepted : 04 December 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: salivary gland tumor,angiogenesis,angiogenic factors,anti-angiogenic factors,histotypes,therapy
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: salivary gland tumor, angiogenesis, angiogenic factors, anti-angiogenic factors, histotypes, therapy

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