Angiogenesis and Cancer
A New Cancer Cure?
There have recently been numerous headlines regarding a new approach to treating cancer and many companies, particularly Entremed, are jumping on the band wagon. The drugs being tested are called "anti-angiogenesis" agents. What are these agents, why the sudden interest and will it really work?
It has long been well known that tumors require a blood supply in order to survive and grow. A solid ball of cells, such as a tumor, would be unable to survive long because nutrients and oxygen would not be able to reach the cells. Many tumors may begin to grow in the body, but will die off unless they are able to attract new blood vessels to grow into them, a process called "angiogenesis". Normally, in a full grown adult, the blood vessels don’t grow very much. However, in growing children and when an adult is injured, chemicals called angiogenic factors will be produced, causing blood vessels to grow towards the area producing the angiogenic factors. Tumors, in order to survive, must also produce such factors to produce their own blood supply.
Dr. Fogelman and the company Entremed were the first to actually take advantage of the absolute requirement of tumors to produce new blood vessels. They identified from rats several factors that can prevent new blood vessel formation—in other words, anti-angiogenic factors. When tested on a large variety of tumors in mice, all tumors tested were arrested and generally regressed. This was an extraordinary result that shows great promise for future cancer treatment. This is an especially promising result since the side effects on an adult animal seem minimal. Furthermore, since tumors so often become resistant to conventional chemotherapy, it is very important to develop new strategies that can supplement and complement traditional methods.
Now some caveats. First of all, the technique has worked only on lab mice and has only been tested under very specific conditions. True, the drugs work on all tumors so far tested, and many have been tested. But there has been some difficulty reproducing the results in other labs. Some can reproduce them, others can’t. A possible reason for this is the fact that lab mice are almost always highly inbred, so that in any given lab the mice used will be almost identical genetically. The variation in mice from lab to lab means that the genetic background in which the experiments are done will differ. The genetic background will affect all aspects of an animal’s biochemistry, and thus will affect how drugs affect that animal. Furthermore, since cancer cells are derived from the animal’s own cells, they, too, will be affected by the genetic background. So, in any given inbred population, a technique may work well, but that is no guarantee that it will work in another population that is genetically different. This is very important since humans are not inbred (no jokes, please!!) and thus there is considerable genetic variation in all human populations when compared with lab mice.
What does this mean? It means, at worst, that the anti-angiogenic agents won’t work on people because they were developed for a very specific case—one particular inbred mouse population. This is unlikely, however. The theory behind the anti-angiogenic agents is still sound and if it can work in one system, it can be adapted to other systems. So what it is more likely to mean is that humans will show a more varied response to these drugs. Like with most drugs, some people will respond well, others won’t respond at all, yet others my be allergic. It is thus important to develop a variety of anti-angiogenic drugs since each one may be effective in a different group of people.
Another possible problem is with children. Since children are actively growing, angiogenesis is necessary for their bodies to develop. So anti-angiogenic agents may be harmful to children and developing fetuses. However, in adults the technique should still be sound, and even for some children, the benefits may outweigh the dangers.
The excitement over these drugs is a little premature, since a great deal more testing is needed. However, I have no doubt that in time Entremed or another company (or many companies) will develop anti-angiogenic agents that either alone or in combination with chemotherapy, surgery or radiation therapy will affect a wide variety of cancers. It will probably not end cancer as a fatal disease, but it will make it far more manageable and may drastically reduce mortality due to cancer. We are seeing a tremendous breakthrough, and the problems that will certainly arise along the way should not detract from our appreciation of this breakthrough.
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