Special Issue "Angiogenesis Inhibitors"

Guest Editor
Prof. Dr. Domenico Ribatti
Dipartimento di Anatomia Umana e Istologia, Università degli Studi di Bari, Piazza G. Cesare 11, Policlinico, 70124 Bari, Italy
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Dear Colleagues,

The idea of targeting angiogenesis to inhibit tumor growth was proposed more than three decades ago by Judah Folkman, and since then several approaches to block or disrupt tumor angiogenesis have been explored.

Antiangiogenesis remains a dynamic and evolving field in oncology. New therapeutic targets continue to emerge followed by the rapid development of new therapeutic agents to be investigated in clinical trials.

Until now, the success of antiangiogenic compounds in the clinic is rather limited when given as monotherapies. This is in contrast with many preclinical results which revealed a much higher efficacy of these agents in animal models.

Prof. Dr. Domenico Ribatti
Guest Editor

Submission Information

All papers should be submitted to pharmaceuticals@mdpi.org. To be published continuously until the deadline and papers will be listed together at the special issue website.

Submitted papers should not have been published nor be under consideration for publication elsewhere. All papers are refereed through a peer-review process. A guide for authors is available on the Instructions for Authors page. Pharmaceuticals is a new international, peer-reviewed, quarterly open access journal published by Molecular Diversity Preservation International.

Article Processing Charges (APC) for publication in this open access journal are waived for well-prepared manuscripts submitted by 30 June 2010. English correction or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those paper accepted for publication, that require extensive additional formatting and/or English corrections.

• angiopoietin-2 antagonists
• antiangiogenic monoclonal antibodies
• assays to validate antiangiogenic agents
• avastin
• biomarkers of response to antiangiogenic therapy
• combination of antiangiogenic therapy with other anticancer therapies
• endogenous inhibitors of angiogenesis
• genetic strategies for targeting angiogenesis
• imaging of tumor angiogenesis
• integrins as targets for antiangiogenic therapy
• metronomic low-dose antiangiogenic chemotherapy
• protein tyrosine kinase inhibitors
• targeted drug delivery to the tumor neovasculature
• thalidomide and its IMiD derivatives
• translating angiogenesis inhibitors to the clinic

Manuscript ID: Pharmaceuticals-angioinhi-20090720-Rusnati-it
Title: Thrombospondin-1 as a Paradigm for the Development of Antiangiogenic Agents Endowed with Multiple Mechanisms of Action
Type of Paper: Review
Authors: Marco Rusnati ^1,*, Chiara Urbinati ¹, Silvia Bonifacio², Marco Presta¹ and Giulia Taraboletti ²
Affiliation: ¹ Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Brescia, 25123, Italy
² Tumor Angiogenesis Unit, Department of Oncology, Mario Negri Institute for Pharmacological Research, Bergamo, Italy; E-Mails: taraboletti@marionegri.it (G.T.); urbinati@med.unibs.it (C.U.); bonifacio@marionegri.it (S.B.); presta@med.unibs.it (M.P.);
* Author to whom correspondence should be addressed: rusnati@med.unibs.it (M.R);
Abstract: Uncontrolled neovascularization occurs in several angiogenesis-dependent diseases, including cancer. The production of endogenous inhibitors during the angiogenic process represents a compensatory response in the attempt to counteract the action of angiogenic growth factors (AGFs). Indeed, neovascularization is tightly controlled by the balance between AGFs and anti-angiogenic agents. The various natural angiogenesis inhibitors identified so far affect neovascularization by different mechanisms of action. Thrombospondin-1 (TSP-1) is a matricellular modular glycoprotein that acts as a powerful endogenous inhibitor of angiogenesis by: sequestering different AGFs in the extracellular environment; inducing an anti-angiogenic program in endothelial cells following CD36 engagement; binding CD47, integrin receptors and proteoglycans (all involved in the angiogenic process). Based on its central and multifaceted role in angiogenesis, TSP-1 has represented a source for anti-angiogenic tools, including TSP-1 fragments, synthetic peptides and peptidomimetics, gene therapy strategies, and agents that up-regulate TSP-1 expression. TSP-1-based inhibitors of angiogenesis, their mechanisms of action and therapeutic potential will be discussed in this review, with emphasis on our experience on AGFs-interacting TSP-1 peptides and the possibility of exploiting them for the design of novel anti-angiogenic agents.
Keywords: angiogenesis, heparan-sulfate proteoglycans, heparin, integrins, interactions, thrombospondin-1