Some potentially VERY BIG NEWS for biotech, cancer sufferers and possible future competition for LGND. I have copied this article from the ENMD thread. I don't know the details of how the company is involved, but I believe this is their treatment. And of course, Nature is a top quality journal. I would not be at all surprised to see a GERN effect in this stock over the next few days, given a couple of doctor's comments in the article. This appears to be a highly effective anti-angiogenisis treatment, which upon repeat applications seems to make the tumors permanently dormant. Of course, it will be at least two years before it enters human trials and anything could happen. Still, very big news IMO. Holds great hope for treating cancer.
>>GLOBE AND MAIL ARTICLE ON JUDAH FOLKMAN AND ENTREMED
Substances that choke cancer tumours reported
Test results using two new-found proteins 'startling'
Thursday, November 27, 1997
By Richard Saltus
The Boston Globe
Dr. Judah Folkman and his colleagues at Harvard Medical School say they have permanently eradicated large tumours in mice
with a combination of two powerful, natural substances that can choke off the blood supply a cancer needs to grow.
The findings, published in the current issue of the journal Nature, are the most dramatic yet in the assault on cancer that Dr.
Folkman conceived more than 25 years ago. Dr. Robert Kerbel, director of cancer-biology research at the Sunnybrook
Health Science Centre in Toronto, called the results so compelling that they could "herald a new era of cancer treatment."
Dr. Folkman said that in one experiment several mice that had received transplanted lung cancers were treated just once, for
25 days, with the two substances angiostatin and endostatin. The tumours regressed completely, and when the mice were
killed after 11 months they were found free of tumours. Subsequent tests have produced even longer cancer-free periods,
virtually the animals' entire lifetimes.
"No one has ever seen anything like this before -- it's a very startling result," Dr. Kerbel said in an interview.
The report in Nature is by Dr. Folkman along with Dr. Thomas Boehm, Dr. Timothy Browder, and Dr. Michael O'Reilly. The
experiments were carried out in the Children's Hospital Surgical Research Laboratory in Boston, which Dr. Folkman heads.
Angiostatin and endostatin are two of the most recently discovered members of a group of proteins called angiogenesis
inhibitors, which block the formation of small blood vessels in the body. If they can successfully be developed as drugs with
few side effects, these substances may be an important addition to anticancer weapons.
In addition to the potent combination of angiostatin and endostatin, the Nature report describes experiments using endostatin
alone that showed mouse tumours did not develop resistance to the drug even after repeated doses. By contrast, tumours
often become resistant -- that is, the drugs become ineffective -- when conventional chemotherapy agents that had originally
been effective are administered again.
While angiostatin and endostatin are too scarce and untried to test in people, the chief executive of a Maryland biotech
company that is developing them as drugs said they may be ready for initial human testing within two years.
The two proteins, both discovered in Dr. Folkman's lab, are part of the chemical system in the body that regulates the growth
of new, small blood vessels that occurs during wound healing and at other times.
Dr. Folkman's insight, which has inspired an entire field of research, was that solid cancer tumours might be starved into
submission by drugs that block the formation of new blood vessels feeding the tumours.
Furthermore, since the drugs attack the blood vessels' endothelial cells instead of the renegade tumour cells themselves, Dr.
Folkman believed the tumours might be less able to evolve resistance to the drugs.
The reason, he said, is that cancer cells are genetically unstable, meaning they easily mutate, or change, so they can evade the
action of the drug attacking them. But the endothelial cells of the blood vessels are more stable and can't quickly evolve into
resistant forms. The new results confirmed that even with long and repeated drug treatment the tumours remained vulnerable,
developing no resistance to the drug.
Dr. Kerbel of the Sunnybrook Health Science Centre said that "what excites me is that we've always been discouraged by this
problem of resistance, and these results provide a glimmer of hope."
Dr. Kerbel wrote in a Nature commentary accompanying the Folkman report: "The results . . . are unprecedented and could
herald a new era of cancer treatment."
When endostatin was administered to rats with tumours and then halted, the researchers found, the tumours remained
vulnerable to the drug throughout several cycles. During periods of treatment, the tumours shrank; when the drug was stopped,
the tumours grew large again. But treatment continued to be effective at all times.
Some of the tumours were equivalent to a human tumour weighing more than 1.3 kilograms, Dr. Folkman estimated.
In a surprising and unexpected finding, the tumours not only remained vulnerable to the drugs but, after cycles of treatment,
inexplicably became dormant and did not regrow.
This occurred after several cycles of endostatin treatment and, what was most impressive, after a single 25-day treatment with
the angiostatin-endostatin combination.
Dr. Folkman said the tumours behave as if they contained some sort of "clock" so that after a given number of treatment cycles
they failed to regrow.<<
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