For brain tumors, origins matter
Sanford-Burnham researchers discover that brain tumors arising from different cell types might require different-and more personalized-treatment approaches Cancers arise when a normal cell acquires a mutation in a gene that regulates cellular growth or survival.
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Since: Dec 05
#1 Nov 15, 2012
This is why Avastin or some other anti-angiogenesis-based cancer drugs may show promise as an aggressive brain cancer drug.
A tumor develops from a single normal cell that has turned cancerous and then continues to divide, creating more cancer cells. At first, these cells can use the nearby blood vessels, but as the tumor grows, some of these cells get further away from a blood supply.
For the tumor to continue growing, it must have a new blood vessel formation or angiogenesis. At a critical point in the growth of a tumor, the tumor sends out signals to the nearby endothelial cells to activate new blood vessels growth.
The growth of the endothelial cells that form the inner lining of the blood vessels is one of the most important steps in establishing new blood vessels.
Two endothelial growth factors, vascualr endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are expressed by many tumors and seem to be important in sustaining tumor growth.
Research has shown that controlling production of new blood vessels can restrict tumor growth, often prolonging the life of the cancer patient.
Anti-angiogenesis treatment is the use of drugs or other substances to stop tumors from developing new blood vessels. Without a blood supply, tumors can't grow freely.
Perhaps the most widely-used anti-angiogenic agent to emerge to date has been the drug Avastin. Avastin targets VEGF that stimulates blood vessel growth. Avastin inhibits the growth of tumors by cutting off their blood supply, which deprives them of oxygen and other nutrients.
Various angiogenesis inhibitors have been developed to target vascular endothelial cells and block tumor angiogenesis.
Volocixmab (Anti-a5ß1 Integrin) is a chimeric antibody that inhibits angiogenesis, including vessel formation induced by VEGF, basic fibroblast growth factor (bFGF), as well as other pro-angiogenic growth factors. The antibody binds to a5ß1 integrin receptors that are present on activated endothelial cells and inhibits the formation of new blood vessels to the tumor, a process that is required for tumors to grow and metastasize.
ABT-510 is a synthetic peptide that mimics the antiangiogenic activity of the naturally occurring protein, thrombospondin-1 (TSP-1). ABT-510 blocks the actions of multiple pro-angiogenic growth factors known play a role in cancer related blood vessel growth, such as VEGF, bFGF, hepatocyte growth factor (HGF), and IL-8.
There has been a biomarker assay developed for microvascular viability to identify potential responders to various anti-angiogenic drugs. It was discovered that endothelial cells are present in tumor microclusters and it appears that drug effect upon these cells can be assessed in the new microvascular viability assay.
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