"The reality is that almost all of the angiogenesis inhibitors have been found to be generic, not to induce drug resistance, to have low toxicity, et cetera, in animals," he adds. "This was first shown with TNP-470 many years ago."

It was Ingber himself who, as a post-doctoral fellow, discovered the drug TNP-470, the first angiogenesis inhibitor from Folkman's lab to enter human clinical trials.

In contrast to newly discovered, highly publicized proteins like endostatin, Ingber says, TNP-470 has actually already been tested in humans in clinical trials conducted since 1992. In April 1998, the first complete tumor remission in a human using this drug was published as a case report in New England Journal of Medicine, and the drug will likely be entering Phase III trials very soon.

Still, Ingber says, "I think Folkman is truly the pioneer in this field and I guess the media feels that if he believes this [endostatin research] is the most exciting thing around, then they should give it their greatest attention. From this perspective, it is a reasonable response."

Long-Term Possibilities

Despite the confused coverage of Folkman's work in the media, Ingber says endostatin has the potential to one day be a very important weapon in the fight against cancer and other diseases.

Endostatin has been shown to induce the complete regression of tumors whereas other drugs may only prevent metastasis or halt growth when used alone.

And theoretically, endostatin patients should be able to undergo long-term treatment with little to no side effects, since the protein occurs naturally in the human body and will therefore not be rejected by the host.

In addition, "many of the drugs which are in clinical trials and which the media has not focused on, also were a direct product of Folkman's work," Ingber says, citing TNP-470 and thalidomide as examples.

But while Ingber gives Folkman due credit, he questions the media's choice of how it focuses its coverage of anti-angiogenesis research.

"The media wants a silver bullet, but it is virtually impossible to obtain one, especially given how cancer trials are designed...using end-stage patients who have failed all other therapies with large tumor mass, et cetera," he says.

Ingber also points out that "sometimes it is a lot easier for the media to sell a simple dream than the complexity of reality."

He explains that the results of Folkman's work so far are based entirely on animal studies, and that most reported human results so far have come from Phase I trials, where the researchers mainly attempt to identify a drug's toxicity while the patients receive escalating doses.

"Since the drug must be given alone in Phase I so that the results are interpretable...no one has seen one hundred percent of tumors regress and disappear when these drugs are given alone," he says. "These are often end-stage cancer patients with tumors that have become modified by many past chemical and radiation therapies."

"This type of result is of no value to the mainstream media because it is not a simple story to sell," he adds.