HER2 Support Group Forums - View Single Post - for those running out of options--sutent promising

gdpawel · 10-06-2008, 05:07 PM

It was discovered that endothelial cells are present in tumor microclusters and it appears that drug effect of Sutent, and other anti-angiogenic drugs, upon these cells can be assessed in a microvascular viability assay.

Endothelial cells, the cells that form the walls of blood vessels, are the source of new blood vessels and have a remarkable ability to divide and migrate. The creation of new blood vessels occurs by a series of sequential steps. An endothelial cell forming the wall of an existing small blood vessel (capillary) becomes activated, secretes enzymes that degrade the extracellular matrix (the surrounding tissue), invades the matrix, and begins dividing. Eventually, strings of new endothelial cells organize into hollow tubes, creating new networks of blood vessels that make tissue growth and repair possible.

Most of the time endothelial cells lie dormant. But when needed, short bursts of blood vessel growth occur in localized parts of tissues. New capillary growth is tightly controlled by a finely tuned balance between factors that activate endothelial cell growth and those that inhibit it.

These new "targeted" drugs mostly need to be combined with active chemotherapy to provide any benefit. You had to take one type of drug for anti-tumor effects of human neoplams, and another drug for anti-microvascular effects. The nice thing about Sutent is that it is an inhibitor of multiple protein kinases involved in both anti-tumor effects and anti-microvascular effects.

Where are the predictive markers that are as useful as ER and Her2? The clinical applicaton of DNA or RNA content assays have been shown to correlate only with response and not survival. How about response and survival? And it would be nice to actually integrate all the gene expression into one convenient test result.

There will be a continuous parade of new "targeted" small and large molecule therapies that will continue to be introduced into the market virutally blind. There should be more use of integrated "targeted" testing to decrease the number of nonresponders (patients who do not benefit from a drug), and increase the number of responders (patients who benefit from a drug).

10-06-2008, 05:07 PM	#7
gdpawel Senior Member Join Date: Aug 2006 Location: Pennsylvania Posts: 1,080	Integrated Targeted Testing It was discovered that endothelial cells are present in tumor microclusters and it appears that drug effect of Sutent, and other anti-angiogenic drugs, upon these cells can be assessed in a microvascular viability assay. Endothelial cells, the cells that form the walls of blood vessels, are the source of new blood vessels and have a remarkable ability to divide and migrate. The creation of new blood vessels occurs by a series of sequential steps. An endothelial cell forming the wall of an existing small blood vessel (capillary) becomes activated, secretes enzymes that degrade the extracellular matrix (the surrounding tissue), invades the matrix, and begins dividing. Eventually, strings of new endothelial cells organize into hollow tubes, creating new networks of blood vessels that make tissue growth and repair possible. Most of the time endothelial cells lie dormant. But when needed, short bursts of blood vessel growth occur in localized parts of tissues. New capillary growth is tightly controlled by a finely tuned balance between factors that activate endothelial cell growth and those that inhibit it. These new "targeted" drugs mostly need to be combined with active chemotherapy to provide any benefit. You had to take one type of drug for anti-tumor effects of human neoplams, and another drug for anti-microvascular effects. The nice thing about Sutent is that it is an inhibitor of multiple protein kinases involved in both anti-tumor effects and anti-microvascular effects. Where are the predictive markers that are as useful as ER and Her2? The clinical applicaton of DNA or RNA content assays have been shown to correlate only with response and not survival. How about response and survival? And it would be nice to actually integrate all the gene expression into one convenient test result. There will be a continuous parade of new "targeted" small and large molecule therapies that will continue to be introduced into the market virutally blind. There should be more use of integrated "targeted" testing to decrease the number of nonresponders (patients who do not benefit from a drug), and increase the number of responders (patients who benefit from a drug).