WHAT IS MEANT BY ANGIOGENESIS???
1.Angiogenesis is nothing but the formation of newer blood vessels. Tumors need blood vessels to grow and spread in the body. (1)
2.This angiogenesis process involves the growth, migration and differentiation of the endothelial cells, which lines inside wall of the blood vessels.
3.The process of angiogenesis is generally controlled by the chemical signals in body. These signals will stimulate both the repair of the damaged blood vessels and also the formation of new blood vessels. Other chemical signals which are,called angiogenesis inhibitors, will interfere with formation of blood vessel. (1)
ROLE OF ANGIOGENESIS IN CANCER:
1.The process of Angiogenesis plays a very critical role in growth and spread of the cancer. A blood supply is essential for tumors to a few millimeters in size.
2.Tumors may cause this blood supply to form by giving the chemical signals which will stimulate angiogenesis. Tumors may also stimulate the nearby normal cells to produce signaling molecules that starts angiogenesis. (1)
3.The resulting new blood vessels will feed growing tumors with oxygen and the nutrients,and allows the cancer cells to invade the nearby tissue, to move all through the body, and to form new colonies of many cancer cells, called as metastases.
4.Because tumors cannot grow beyond a particular size or spread without blood supply, scientists are trying to find different ways in orderto block tumor angiogenesis.
5.They are studying natural and synthetic angiogenesis inhibitors, which are also called antiangiogenic agents, with the idea that these molecules will prevent or slow the growth of the cancer cell. (1)
MECHANISM OF ACTION OF ANGIOGENESIS:
Angiogenesis involves the binding of the signaling molecules, such as the vascular endothelial growth factor (VEGF), to the receptors on the surface of the normal endothelial cells. When VEGF and other endothelial growth factors bind to their corresponding receptors on endothelial cells, signals within these cells are initiated that will promote the growth and survival of the new blood vessels. (1)
These ANGIOGENESIS INHIBITORS agents,will interrupt the critical cell signaling pathways that is involved in the tumor angiogenesis and growth, and it comprises of 3 primary categories: (2)
1. monoclonal antibodies-these mca's are directed against the specific proangiogenic growth factors and/or their corresponding receptors ex: bevacizumab, Cetuximab
2. small molecule tyrosine kinase inhibitors (TKIs) ex: Erlotinib, Pazopanib, Sorafenib, Sunitinib (2)
3. inhibitors of mTOR(mammalian target of rapamycin) ex: Temsirolimus, Everolimus
Angiogenesis inhibitors interfere with the various steps in this process.
For example, bevacizumab (trade name:Avastin(r)) is a monoclonal antibody that will specifically recognizes and binds to the VEGF. When VEGF is attached to the bevacizumab, it is unable to activate the VEGF receptor. Other angiogenesis inhibitors, including sorafenib and sunitinib, bind to receptors on the surface of endothelial cells or to other proteins in the downstream signaling pathways,thereby blocking their activities (1)
CURRENTLY USED ANGIOGENESIS INHIBITORS:
1.The U.S. Food and Drug Administration (FDA) has approved a drug named bevacizumab which is to be used alone for glioblastoma .Bevacizumab was the 1st angiogenesis inhibitor that was Confirmed to slow the tumor growth and mainly, to extend the lives of patients with some cancers. (3)
3.Sorafenib is approved for hepatocellular carcinoma and kidney cancer,.
4.sunitinib and everolimus are approved for both kidney cancer and neuroendocrine tumors.
5.pazopanib exclusively for kidney cancer.
ANGIOGENESIS INHIBITORS----THEIR UNIQUE CHARACTERISTICS
1.Angiogenesis inhibitors are the unique cancer-fighting agents as they tend to inhibit the growth of the blood vessels rather than that of the tumor cells. In some types of cancers, angiogenesis inhibitors are more effective when combined with additional therapies likechemotherapy. (3)
1.http://www.cancer.gov/cancertopics/factsheet/Therapy/angiogenesis-inhibitors(accessed on 2-11-11:12.30a.m)
2.http://www.angio.org/understanding/inhib.php(accessed on 2-11-11:12.30a.m)
3.http://cancer.stanford.edu/information/cancerTreatment/methods/angiogene...(accessed on 2-11-11:12.30a.m)
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