American Association for Cancer Research

Anti-Angiogenesis Drugs




One of the most exciting and most important advancements in cancer treatment in the last two to three years has been the addition of drugs called anti-angiogenic therapies to chemotherapy. These anti-angiogenic agents—such as Avastin (bevacizumab) from Genentech and two other drugs—have been recently approved by the FDA. Trials are showing that when they are added to chemotherapy, these drugs can increase lifespan on average by two to five months in colorectal cancer, lung cancer, kidney cancer and a type of stomach cancer known as GIST (gastrointestinal stromal tumor).

It was originally thought that the purpose of anti-angiogenesis agents would be to starve a tumor to death. However, the best outcome in the clinic has come when anti-angiogenic therapy is combined with chemotherapy. Now think with me for a few seconds: What do we need to deliver chemotherapy to a tumor? The answer is: We need blood vessels. If we kill blood vessels with anti-angiogenic therapy, how can we get these unprecedented results in survival when we give the anti-angiogenic therapy with chemotherapy? To me this seems paradoxical.

To resolve this paradox, in 2001 I put forward a counterintuitive idea. I proposed that anti-angiogenic therapy, in addition to destroying some blood vessels, improves the structure and function of remaining blood vessels. So suppose we started out with 100 blood vessels, just an arbitrary number. With anti-angiogenic therapy, we kill 50. I proposed that the remaining 50 blood vessels become more organized or well-structured. Therefore, chemotherapy—designed to kill the cancer cells—is more effective when used with the anti-angiogenic drugs.

I'm going to tell you how we came up with this idea and why it is important.