We discussed in Hallmark #5 how tumors produce growth factors that stimulate new blood vessels to grow (a process called angiogenesis). These new blood vessels provide the growing tumor with oxygen and other nutrients. We also talked about how the development of new blood vessels is only turned on briefly during certain periods such as wound healing and menstruation. So, the next logical step would be to ask how we can stop the growth of new blood vessels (inhibit angiogenesis) in an attempt to “starve” the tumor.
Interest in this area is not new and research and studies have been ongoing for decades. There are approximately 15 proteins that are involved in angiogenesis, so to say it is a complex system that must be kept in tight balance is an extreme understatement. Not long ago, angiogenesis inhibitors were touted as the magic bullet to kill all cancers. Indeed, the preclinical (animal studies) data looked good and researchers and doctors were encouraged. Early phase clinical testing showed the drugs to be relatively safe, but the actual effectiveness of this class of drugs against tumors has left a lot to be desired, especially in pediatrics. Many drugs in this category have received FDA approval. They are often used in conjunction with other chemotherapy agents for adult cancers, but none have proven significant benefit in the majority of pediatric cancers to be moved into first line therapy.
The less-than-stellar performance of these drugs is likely linked back to the number of proteins involved in this complex process. 15 proteins coordinating together to promote one process has built-in redundancy. For example, if you knock one, two, or three of the proteins out with a drug, the other 12 proteins may increase or take over the function of the few that were blocked. Additionally, it is likely that tumors require different angiogenesis growth factors at various stages of growth and so it may be a moving target. Nonetheless, trials are still ongoing looking at these drugs in combination as there is still hope and data that they may be beneficial in the right mix for the right tumor.
#morethanfour #ChildhoodCancer365
