[gdpawel]

Truly sad news for a great researcher, scientist and physician. Nobody believed Folkman that the growth of cancers could be stopped, even reversed, by blocking the tiny vessels that feed them blood. Over the years, however, he had survived peer rejection of his theory and gone on to develop drugs that did what he predicted they would do. His ideas will be greatly missed.

There are some scientists that believe the realization of Dr. Folkman's brilliant dream of inhibition of angiogenesis is not sufficient to consistently control cancer. There are multiple ways by which tumors can evolve that are independent of angiogenesis. Tumors can acquire a blood supply by angiogenesis, but some say also by co-option of existing blood vessels, and vasculogenic mimicry. All must be inhibited to consistently starve tumors of oxygen.

Vascular co-option is the invasion of malignant cells along blood vessels. Instead of growing new blood vessels, tumor cells can just grow along existing blood vessels. This process cannot be stopped with drugs that inhibit new blood vessel formation. Vasculogeneic mimicry is where some types of cancers form channels that carry blood, but are not actual blood vessels. Drugs that target new blood vessel formation also cannot stop this process.

All three of these processes involve the use of normal cellular machinery to carry out proliferation and invasiveness. The consistent and specific control of cancer requires therapy that can target the set of all malignant cells that could evolve. It is critical that each drug be given at a dose sufficient to kill all cells that express the pattern targeted by the individual drug. That requires that all three mechanisms be addressed.

Folkman had stated that angiogenesis inhibitors will not be the cure for cancer but that they will make cancer more survivable and controllable, especially in conjunction with other treatments. These new targeted drugs mostly need to be combined with active chemotherapy to provide any benefit and the need for predictive tests allowing for a rational and economical use of them for individualized therapy selection has increased.

Look at what researchers did with Folkman's discovery of endostatin. When is was first discovered, doctors hoped its tumor-fighting properties would lead to a cure for cancer. But clinical trials had been disappointing, possibly because most clinicans had injected the hormone directly into patients, where the hormone broke down in the body before it had a chance to slow the spread of cancer.

I can understand the disbelief that endostatin clinical trials had been disappointing. But researchers like Dr. Veena Antony, at the University of Florida, rethought the situation by understanding that talc had the ability to stunt cancer growth by cutting the flow of blood to metastatic lung tumors. Her study, published in the Europen Respiratory Journal, reveals that by allowing talc in the chest cavity, it causes normal cell to produce 10-fold higher levels of endostatin, a hormone released by healthy lung cells, and inhibiting the growth of tumors.

Thanks to scientists like Folkman and Antony, who took the time to think through "whiz bang" science that often gets a pass without much thought. The problem is that few scientific discoveries work the way we think and few physicians/scientists take the time to think through what it is they've discovered.

Dr. Antony is still having a hard time getting funding for the research. It is hard to get the NCI to think outside the box. However, here and there around the world, there are decisions still being made by folks who aren't in the pockets of American Big Business. Individual intelligence, integrity and curiosity.