Editorial [Hot Topic: Angiogenesis and Anti-Angiogenesis (Executive Editor: Maurizio Botta)]

In the first contribution to this special issue of Current Pharmaceutical Design dedicated to topics on angiogenesis and anti-angiogenesis, Presta and co-workers [1] describe the FGF/FGFR as a target for anti-angiogenesis therapy, starting from the experimental evidence that the FGF family is involved in angiogenesis and angioproliferative diseases. On this basis, they summarize different approaches aimed at impairing FGF/FGFR activity and their possible involvement in therapeutic protocols. In the same context, Guerrini and co-workers [2] review on conformational aspects of heparin sequences involved in the interaction with FGF. For this purpose, results from both experimental (X-ray crystallography and NMR) and theoretical (molecular modeling simulations) studies are reported for heparin oligosaccharides of variable length, as well as for heparins bearing “glycol-split” residues. Glicol-split heparins are also reported by Casu and co-workers [3] as potent inhibitors of heparanase and, most interestingly, as antiangiogenic and antimetastatic drug candidates. Moreover, they also allow to distinguish antiangiogenic effects caused by heparanase inhibition from those deriving from direct inhibition of growth factors. The next contribution describes compounds with antiangiogenic activity. Peptides derived from endogenous proteins (i.e., thrombospondin, laminin, endostatin, decorin, and parathyroid hormone) are examples of antiangiogenic agents reported by Ge and co-workers [4]. They could be obtained following phage-display library screening and combinatorial chemistry, with physico-chemical profiles appropriately set up to increase their potency and stability. However, application of such compounds into clinical practice is not obvious, but critical problems are to be solved before. Rossello and co-workers [5] report a survey on inhibitors of matrix metalloproteinases (MMPi), focusing attention on compounds with improved potency and selectivity. Improvement of binding to the catalytic zinc atom, design of no-zinc binding inhibitors and dimeric inhibitors are the new and major challenges in the field of MMPi. In the contribution from Hiraki and co-workers [6], a couple of type II transmembrane glycoproteins (namely, chondromodulin-I and tenomodulin) are described as inhibitors of angiogenesis and anti-tumorigenic agents. Details on structure, biological activity and localization are also reported. Miura and co-workers [7] discuss on the regulation of angiogenesis and angiogenic factors by cardiovascular medications (such as statins, angiotensin II receptor blockers, ACE inhibitors, and calcium channel blockers) in the context of coronary artery disease (CAD). The development of coronary collateral circulation is reported to have a critical role for treating patients with CAD. Schenone and co-workers [8] report on Src inhibitors able to interfere directly with angiogenic processes, while Angelucci and his group [9] describe the role of the Focal Adhesion Kinase (FAK) and the Proline-rich tYrosine Kinase-2 (PYK-2) in angiogenesis. These two topics are becoming very important in the studies on modulation of angiogenesis and represent a new avenue for the search of antiangiogenic small molecules. References [1] Rusnati M, Presta M. Fibroblast growth factors/fibroblast growth factor receptors as targets for the development of anti-angiogenesis strategies. Curr Pharm Des 2007; 13(20): 2025-2044. [2] Guerrini M, Hricovini M, Torri G. Interaction of heparins with fibroblast growth factors. Conformational aspects. Curr Pharm Des 2007; 13(20): 2045-2056. [3] Vlodavsky I, Ilan N, Naggi A, Casu B. Heparanase: Structure, biological functions, and inhibition by heparin-derived mimetics of heparan sulfate. Curr Pharm Des 2007; 13(20): 2057-2073. [4] Sulochana KN, Ge R. Developing antiangiogenic peptide drugs for angiogenesis-related diseases. Curr Pharm Des 2007; 13(20): 2074-2086. [5] Nuti E, Tuccinardi T, Rossello A. Matrix metalloproteinase inhibitors: New challenges in the era of post broad-spectrum inhibitors. Curr Pharm Des 2007; 13(20): 2087-2100.....