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ANGIOGENESIS INHIBITORS TACKLING VASCULARIZATION

by Selleckchem | Mar 13 2012

THERAPIES AGAINST ANGIOGENESIS:

During normal cellular growth patterns new blood vessels are formed to provide a vascular network to enable nutrients and oxygen enter and for waste to leave the system. This process is referred to as Angiogenesis. Tumors are unregulated cellular growths but they still require oxygen and nutrients to be able to grow, depriving tumors of either oxygen or nutrients would halt tumor growth or trigger tumor reduction through apoptosis. Since tumors are unregulated growth they require a more efficient or extensive vascular system than normal tissues hence angiogenic processes represent a possible chemotherapeutic target with angiogenesis selective inhibitors. Research has demonstrated over twenty different factors that regulate angiogenic processes providing a rich source of potential targets for angiogenesis pathway inhibitors. These all angiogenesis antagonists and either directly or indirectly affect the angiogenic processes. Angiogenesis inhibition takes advantage of known factors to develop precisely-structured proteins with known biological effects. Angiogenesis inhibitor drugs. can consist of small molecules such Marimastat or modified proteins such Bevacizumab.

Angeneosis inhibitors, cancer and their potential uses:

Bevacizumab - Bevacizumab is marketed under the trade name Avastin by Genetech and Roche. It is widely used in colorectal, NSCLC, breast, kidney cancers and in glioblastomas. Bevacizumab is a monoclonal antibody that was derived from a mouse model that has been adapted for use in the human system.[9] Bevacizumab does not appear to be able to cure any form of tumor development but has significantly prolonged the life of many subjects. Typically Bevacizumab is used in combination with traditional chemotherapy with some notable success [10-14]. The disadvantage of Bevacizumab is its very high cost, $100, 000 per patient for approximately 2-3 months extended life. Most insurance companies and medical services do not fund Bevacizumab treatments due to the extremely high cost.

Marimastat – Marimastat was introduced in 1998 as an inhibitor targeting matrix metalloproteinases [15] which are proteins that degrade extracellular matrix proteins and certain biological molecules. Marimastat was a broad spectrum inhibitor but despite initial pre-clinical promise responded badly upon introduction into the clinic [16-24]. Marimastat was discontinued in 2005 but maintains a presence as a research probe into the mechanisms behind MMP inhibition.

BAY 12-9566 - BAY 12-9566 is matrix metalloproteinase (MMP) inhibitor developed by Bayer, Germany. Angiogenesis inhibitors in clinical trials demonstrated that Bay 12-9566 halted invasion by endothelial cells in a manner that was dependant on applied concentration. Clincally Bay 12-9566 demonstrated abilities to inhibit the number and volume of lung metastases but all clinical trials for this compound has been stopped and further clinical investigation is planned. [25-31]

Thalidomide – Thalidomide is a name known to the world as monster in the pharmacological industry. Poor quality research meant that Thalidomide was introduced into the market while processing disastrous teratogenicity and neuropathy. The mechanisms behind the side effects observed with Thalidomide are exactly the same as those creating interest in its anti-angiogenesis properties. Thalidomide has been reported pre-clinically as being active in prostate cancer, glioblastoma, lymphoma, arachnoiditis, Behçet's disease, and Crohn's disease. Clinically Thalidomide is approved for used in combination therapy with dexamethasone for multiple myeloma, it is under investigation at phase 1 and 2 levels in combination with tmozolamide, gemcitabine, oxalaplatin, epirubicin, cyclophosphamide and carboplatin. Many clinical trials show increased benefits of including Thalidomide in the combination and phase 3 trials involving Thalidomide are in progress indicating a new lease of life for this misused molecule.[32]

One can buy angiogenesis inhibitors from any supplier.

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