Editorial [ Anti-Angiogenesis Agents Executive Editor: Cezary Marcinkiewicz ]

Angiogenesis is a process of new vessels formation from preexisting vasculature. This process is important in organ development during embryogenesis and less significant for the physiology of adult organisms. However, pathological angiogenesis has been observed in many diseases and is starting to be considered as a pharmaceutical target for therapy. A major effort has been initiated in developing angiostatic drugs for inhibition of cancer progression, but in other disorders including inflammatory and eye diseases, clinical trials testing angiogenesis inhibitors have also been initiated. The new pharmaceuticals have been designed based on the structure of endogenous regulators of angiogenesis as well as natural products isolated from plants and animals. The review papers presented in this issue of the journal summarize approaches that are currently focusing on clinical application of angiogenesis modulators and also provide a general overview of the mechanisms that could be important in angiogenesis related complications during therapy. In the first two papers the authors discuss the modulation of angiogenesis by endogenous factors and how this event may affect pathological angiogenesis. The article provided by Colman [1] summarized the efforts that have been undertaken to characterize the relationship between angiogenesis and the kallikrein-kinin system. The major component of this system bradykinin (BK) participates in positive regulation of angiogenesis, whereas the kinin-free derivative of high molecular weight kininogen (HKa) has been characterized as an angiogenesis inhibitor. The active domain (D5) of HKa and the antibody that blocks binding of high molecular weight kininogen (HK) to endothelial cells inhibited experimental tumor growth as well as inflammatory arthritis and bowel diseases. The targeting of kallikrein-kinin system in inhibition of angiogenesis seems to be a very exciting new paradigm in cancer and inflammatory diseases therapy. Further studies are required to explain the mechanisms underlying this approach. A very interesting paper is presented by Lazarovici and his colleagues [2]. The authors broadly discuss the importance of vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) in cardiovascular and nervous systems, focusing on the seemingly independent, yet interrelated problems of angiogenesis and neurogenesis. The observation that VEGF may directly affect neuronal outgrowth and provide neuroprotection, while NGF may regulate angiogenesis, suggests the existence of an effective cross-talk between the vascular and the nervous system. These growth factors bind to specific receptors that have been found on both neurons and endothelial cells. Thus, they may act as complementary elements which might be essential for the protection and functioning of both the vascular and nervous systems. In this light, the use of selective blockers of VEGF and NGF receptors that are currently in clinical trials may be re-considered in a new realm, a paradigm shift. For example, the synthetic small compound K252a that binds to the NGF-specific receptor trkA, may be applied as an angiostatic drug in cancer therapy. As a caveat, pharmacological modulation of one system may have harmful side effects on the other system. Thus, blocking of angiogenesis in cancer therapy may initiate and develop neurodegradative processes, while neuroprotective therapy in Alzheimer' and Parkinson's diseases may induce pathological angiogenesis resulting in development of cancer. Based on this, the clinical trials involving blockade of VEGF and NGF function should carefully monitor side effects of the nervous and vascular systems, respectively. The general overview of inhibitors of angiogenesis that are currently in clinical trials are provided by Verhoef et al. [3]. Special attention of the authors is focused on the application of anti-angiogenic compounds in clinical oncology. For this reason, the multimodality treatment in clinical practice, involving the cooperative activity of surgeons, radiotherapist and medical oncologists, is raised as an attractive strategy for fighting cancer. All possible difficulties that may occur during angiostatic therapy are emphasized and discussed, as well as benefits of this cooperative approach are broadly described. Although the majority of anti-angiogenesis agents are developed for treatment in oncology, the angiostatic therapy may be significant for other diseases. The next two review articles discuss possible applications of angiostatic pharmaceuticals in autoimmune disease such as arthritis [4], and eye diseases such as diabetic retinopathy or age-related macular degeneration [5]. Bainbridge et al. [4] presented the bulk of anti-neovascularization compound in clinical and pre-clinical trials with respect to use in therapy of rheumatoid arthritis (RA). This kind of therapy may be an alternative approach to anti-cytokine treatment in RA..........