Folkman's Cancer Cure Research Finally Duplicated by Government Lab

For Harvard Medical School (HMS) Professor M. Judah Folkman--once touted as the man who would cure cancer, then maligned when his research couldn't be duplicated--this week held the first good news in a long time.

Folkman, who is Andrus professor of pediatric surgery at HMS, was catapulted into the national spotlight last May, when the New York Times reported that he had been able to eliminate tumors in mice.

But then researchers at the National Cancer Institute (NCI) couldn't get the same results and Folkman's methods were questioned in a Wall Street Journal article last November. Last week, Folkman's situation seemed to hit a new low as pharmaceutical company Bristol Myers Squib (BMS) announced they would no longer seek to produce the drugs Folkman developed.

And after months of tinkering, last Wednesday his saga finally took a positive turn as NCI confirmed some of Folkman's results. But the research will continue, and it will likely be some time before Folkman's research can be confirmed or rejected for certain.

Folkman's research works with compounds designed to shrink tumors by restricting their blood supply.

He and his team worked from the simplistic theory that without its own blood supply, a tumor could not grow beyond minuscule size.

And, according to results Folkman published in a medical journal in November 1997, these methods eradicated tumors in laboratory mice--surpassing his original goal of simply shrinking the tumors.

This resulted in a flood of initial publicity, capped by a New York Times cover story in which Nobel laureate and co-discoverer of DNA James D. Watson was quoted as saying that Folkman would have the cure for cancer in two years.

Watson later issued a clarification, saying he was still hopeful but backing away from promises of a cure.

Folkman himself was also quick to caution that the discovery of a cure was not imminent.

In an oft-quoted remark made to the New York Times, Folkman quipped, "If you have cancer and you are a mouse, we can take very good care of you."

As Folkman's story gained national prominence, NCI--part of the National Institutes of Health--set out to duplicate his research.

But intensive NCI trials were unable to successfully reduce tumors in mice, and questioning of Folkman's results intensified this fall.

When evaluating scientific research, results can not be given full credence until they have been independently duplicated.

This presents problems because the methods and compounds used in the experiments are often sensitive and difficult to reproduce.

Folkman answered the fall's doubters with a press release that said he remained hopeful his results would be replicated and that the transferring of techniques between laboratories is often painstaking and time-consuming.

At that point, Folkman and NCI formulated a plan for collaboration between researchers from their labs that would speed the process up.

But in another blow for Folkman last Tuesday, BMS--which had contracted to produce one of the drugs Folkman uses in his cancer treatment--pulled out of that agreement.

But one day later, NCI researchers announced that they had been able to reduce tumor size using one of Folkman's drugs, endostatin.

To achieve tumor reduction, Folkman's treatment inhibits angiogenesis, the growth of blood vessels within the tumor. Two of the main drugs used are named endostatin and angiostatin.

While Folkman's strongest results were achieved using a combination of these two drugs, NCI's confirmation regards only endostatin.

This duplication clears the way for what the public has been clamoring for since last May--human trials.

Initially, endostatin will undergo Phase I human trials, meaning that the object will be to determine only its safety and the appropriate dosage schedule.

Very few human subjects will be approved for these trials, and the tumors treated will be restricted to solid masses, such as those found in the breast or colon.

Researchers at the NCI caution against runaway expectations--the time needed to adapt the technique from mice to humans will be considerable.

There are currently more than a dozen compounds in development that hope to treat cancer through similar attempts at inhibition of angiogenesis, all used by different researchers across the country.

As is typical in institutional research, all compounds devised by Folkman become the property of his employer, Children's Hospital.

Both endostatin and angiostatin were licensed to the pharmaceutical company EntreMed, and angiostatin was further licensed to BMS.

In response to BMS's announcement that they would not produce angiostatin, EntreMed's stock plummeted, only to be revived after the NCI announcement one day later.

EntreMed can now attempt to produce angiostatin itself, as it does endostatin, or license it to another company.