Researchers in California and Rockville said yesterday that they had discovered two new proteins that can block the growth of blood vessels, adding to the growing list of compounds that may attack cancer by cutting off tumors' blood supplies.
The discovery was made by a team led by Luisa Iruela-Arispe, a molecular biologist at the University of California at Los Angeles, and reported in a forthcoming issue of the Journal of Biological Chemistry. She collaborated with researchers at Human Genome Sciences Inc. of Rockville, where the genes that tell cells how to make the two proteins were discovered.
"Research in this area is important," Iruela-Arispe said. "But I don't think we're going to find the cure tomorrow. We're going to conquer tumors in steps."
The discovery could be bad news in the long run for EntreMed Inc. of Rockville, whose efforts to attack the blood supply of tumors have gained wide attention and investor interest. One of the new proteins is said by its discoverers to be 10 times as potent at blocking blood vessels as EntreMed's most advanced compound.
The field in which Iruela-Arispe labors came to wide attention last year when an article in the New York Times spotlighted two drugs under development by EntreMed. Some scientists quoted in the article implied that a cancer cure might be just around the corner, but this has not proved to be the case.
EntreMed, which had not sought the publicity and wasn't prepared for the media frenzy that followed, has seen its stock whipsawed over the past 18 months as market sentiment ebbed and flowed with each incremental development in the field. Only now is the company preparing to begin human testing of its drugs, which could take years.
The newly described proteins, dubbed METH-1 and METH-2, appear to be part of the body's natural mechanism for controlling the growth of blood vessels. Such growth is critically important during childhood, during wound healing and in a few other circumstances, but it is relatively rare in healthy adults.
Tumors are able to grow large because they somehow induce the body to sprout new blood vessels to feed them oxygen and other nutrients. A worldwide search is under way to find compounds that block the growth of blood vessels and then to test those compounds in cancer patients.
Blood-vessel growth is known as angiogenesis, and compounds that block it are called angiogenesis inhibitors. In animal tests, METH-1 is proving to be a particularly potent inhibitor. Iruela-Arispe's group said it was about 10 times as powerful as endostatin, a protein on which EntreMed hopes to begin human tests later this year.
"We're excited," said William Haseltine, chief executive of Human Genome Sciences, which retains commercial rights to the new compounds. He emphasized, however, that it was far too early to say which inhibitors might ultimately be useful in human cancer treatment.
John W. Holaday, chief executive of EntreMed, called the comparison of METH-1 to his company's drug "entirely premature." He noted that METH-1 and METH-2 had not yet been tested in animals with cancer, much less in people.
"We've never built our company by trying to tear down competing products," he said. "You never really get anywhere that way."
Iruela-Arispe, like other scientists in the field, contends that the ideal treatment strategy may eventually involve "cocktails" of drugs that block growth of blood vessels. What such a development would mean for the fortunes of individual companies is, for now, anyone's guess.
Shares of EntreMed closed yesterday at $22, up $1.12 1/2. Shares of Human Genome Sciences closed at $56.68 3/4, up $1.18 3/4.