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Blood is transported in the body via blood vessels that form intercalated network of arteries, veins and capillaries. The normal process of growth and development of growth and development of new blood vessels form the pre-existing ones is called as angiogenesis. Angiogenesis is a normal process in the development, wound healing etc. However, the abnormal proliferation of blood vessels has been implicated in more than 20 twenty diseases including cancer. Such diseases that are related to angiogenesis can be treated by the use of angiogenesis inhibitors. Pathological Angiogenesis Angiogenesis allows the growth of blood vessels in normal conditions however when it becomes associated with a disease, it is called as pathological angiogenesis. Pathological angiogenesis may start in a cell that is deprived of oxygen. Oxygen deficiency stimulates the release of angiogenic molecules which attract inflammatory and endothelial cells. Inflammatory cells intensify the angiogenic stimuli which cause the differentiation of endothelial cells. Also, endothelial cells start secreting matrix metalloproteases (MMP) that digest the walls of blood vessels and allow them to migrate towards the site of angiogenic stimuli. The breakdown of walls of vessels further intensifies the inflammatory response. As a result, variety of secreted proteins adheres together and forms a capillary tube. Such capillary tubes provide a route for continuous blood flow even to the tumor cells. Role of Pathological Angiogenesis in Cancer Angiogenesis plays a key role in the progression of cancer. Very small tumors can survive without direct blood supply. However, in order to grow large in size and even metastasize, the tumor needs blood supply that is provided by angiogenesis. The tumor cells divide fast and uncontrollably and become deprived of oxygen. They start producing growth factors which stimulate inflammatory response and help in the establishment of capillaries providing direct blood supply as shown in the following figure [1]. Angiogenesis finds its relation with different types of cancer including colon cancer, renal cancer, breast cancer etc. This is the reason that when the relation of angiogensis to cancer is found in a particular patient, angiogenesis inhibitors (e.g. sorafenib, axitinib, sunitinib etc.) prove to be very useful in preventing tumorogenesis. Regulators of Angiogenesis Development of angiogenesis in the body is attributed to more than 20 endogenous regulators of angiogenesis which mainly include: Growth factors (VEGF, FGF, EGF, TGF-beta): Among these regulators growth factors especially, VEGF (vascular endothelial growth factor) are very important target of the compound libraries used for drug designing. Matrix metalloproteases (MPP): Matrix metalloproteases are zinc dependant endopeptidases that can degrade extracellular matrix proteins. The endogenous inhibitors of MMPs are called as TIMPs (tissue inhibitor of metalloproteases). Synthetic inhibitors have also been developed including BAY 12-9566, marimastat, AG3340 etc. Combination therapies are under clinical trials e.g. marimastat plus gemcitabine for pancreatic cancer, AG3340 with taxol for lung cancer etc. Cytokines: Cytokines are small cell signaling proteins that may orevent angiogenesis by decreasing the production of angiogenic growth factors. Integrins: Integrins are the transmembrane receptors that regulate intracellular processes on activation. Integrins regulate adhesion, proliferation, migration and survival of cells. Various types of mutations can lead to abnormal signaling in integrin mediated pathways, thereby promoting angiogenesis. Inhibitors of integrin can also prove to be useful in preventing angiogenesis [2]. Conclusion In a nutshell, angiogenesis plays an important role in the proliferation and spread of cancer. It has also been linked to other ailments including cardiovascular disease. High throughput screening and virtual screening of the possible angiogenesis regulators in cancer cells can be used for the development of new inhibitors to prevent a variety of cancers. Screening of compound libraries can be highly useful in exploring new targets to inhibit angiogenesis and bringing newer drugs in the market! As one of the world leading suppliers of high-performance life-science products. We have over 8,000 products which consist of inhibitors, antibodies, RNAis, proteins and peptides those which focus on signaling pathways such as Lapatinib, Pazopanib, Temsirolimus & so on. Furthermore, compound libraries for high-throughput screening and high-content screening are also available.
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