Angiogenesis therapy

As of today, Cediranib (AZD2171) has the potential to be a best in class angiogenesis therapy. It is one of a new generation series of orally available, highly potent inhibitors of KDR kinase. The compound inhibited VEGF-stimulated HUVEC cell proliferation with an IC50 value of 0.4 nM and was specific for this type of proliferation. 

Harris AL. Anti-angiogenesis therapy and strategies for integrating it with adjuvant therapy. Recent Results Cancer Res 1998 152 341-352. 

Kornowski R, Leon MB, Fuchs S, Vodovotz Y, Flynn MA, Gordon DA, Pierre A, Kovesdi I, Keiser JA, Epstein SA. Electromagnetic guidance for catheter-based transendocardial injection a platform for intramyocardial angiogenesis therapy. Results in normal and ischemic porcine models. J Am Coll Cardiol 2000 35 1031-1039. 

The lack of gene expression is another potential barrier. Some systems for inducible gene expressions have proved to be effective and safe in animal models (31), but they have not yet been tested in humans. Recent advances in stem cell research provide the possibility of combining gene therapy with ex vivo gene transfer into stem cells for angiogenesis therapy, as will be discussed later, If successful, this approach may overcome most of the obstacles presented by gene therapy. 

S.E. Epstein, R. Komowski, S. Fuchs, and H.F. Dvorak, Angiogenesis therapy amidst the hype, the neglected potential for serious side effects, Circulation 104, 115-119 (2001). 

Rafii, S., et al. 2002. Vascular and haematopoietic stem cells novel targets for anti-angiogenesis therapy Nature Rev. Cancer 2 826-835. 

Alternatively, if the tumor vasculature could be made the target, then the drugs would not have to cross the vessel wall or the interstitium. Anti-angiogenesis therapy, pioneered by Judah Folkman (1993), whose aim is to stop the growth of new vessels of a tumor, is a successful example of such an approach. Hyperthermia, photodynamic therapy, and cytokines such as TNF are other approaches which may also impair the tumor blood supply. One attractive hypothesis is that when several of the current cytotoxic therapies work, it is not only because they destroy cancer cells, but also because they may destroy a solid tumor by impairing its blood supply. Thus judiciously combining anti-vascular therapies with anti-cellular therapies may lead to synergistic results. Our recent study with lym-... 

Tao X, Sood AK, Deavers MT, Schmeier KM, Nick AM, Coleman RL, Miiojevic L, Gershenson DM, Brown J. Anti-angiogenesis therapy with bevacizumab for patients with ovarian granulosa ceil tumors. Gynecol Oncol 2009 114(3) 431-6. 

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