Targeting Vascular Endothelial Growth Factor

In a study examining 64 resected breast cancer specimens, researchers looked at the degree of expression of various pro-angiogenic factors (24). While it was found that all specimens expressed at least six of the factors considered, the expression of VEGF in these tumors exceeded all other factors in the majority of specimens. On the basis of these and similar findings in translational work, many have concluded that VEGF may in fact be the key regulatory factor in angiogenesis, and perhaps by specifically targeting this pathway one could "turnoff" the angiogenic switch (1,11). This has launched a series of efforts aimed at potentially targeting the VEGF ligand, its receptors, intracellular receptor tyro-sine-kinase domains, or the associated downstream signaling mediators, all with the hope of halting pathologic angiogenesis. While many approaches are still under investigation, the most studied and successful to date involves the development of a monoclonal antibody directed against the VEGF-A isoform, the most predominant and active ligand in this pathway. Initial efforts yielded promising results with demonstrable in vivo inhibition of tumor growth by the administration of an anti-VEGF monoclonal antibody (25). Subsequent studies confirmed these findings in a variety of cell lines, each showing that the addition of anti-VEGF antibodies could successfully block angiogenesis and inhibit in vivo tumor growth (26-28). This work has lead to the development of a humanized, monoclonal antibody directed at the VEGF-A ligand that has gained considerable attention in recent years, particularly in the treatment of breast cancer. Bevacizu-mab (AvastinĀ®, Genentech, San Francisco, CA) is currently the only FDA-approved monoclonal antibody aimed at specifically inhibiting angiogenesis in solid tumors (29). Bevacizumab has been shown to effectively bind the soluble VEGF-A ligand, preventing binding to its receptors (Flt-1 and KDR/Flk-1), and essentially disrupting the initial signal in the angiogenic cascade. While bevacizu-mab is currently only approved for use with bolus IFL (irinotecan, 5-FU and leucovorin) in first-line therapy for metastatic colorectal cancer (30), it has shown potential in early trials investigating its use in nonsmall lung cancer (31), renal cell carcinoma (32), and breast cancer. In breast cancer studies, the benefits of adding this agent are still being evaluated, but much of the preliminary data suggests a role in both the metastatic and adjuvant settings.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

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