TIME EUROPE
January 15, 2000, Vol. 157 No. 2
The Hunt for Cures
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Glivec is just one of several new therapies that work by cutting a cancer cell's lines of communication, either preventing it from reproducing or forcing it to self-destruct. Other signal-jamming treatments use monoclonal antibodies, tiny proteins that resemble the human immune system's own antibodies but that bind to the surface of cancer cells. New York City-based ImClone Systems has an antibody called imc-c225, now in the final phases of testing in colorectal and head and neck cancer, that acts like bubble gum stuffed in a keyhole. It prevents a specialized protein known as a growth factor from fitting into a slot on the surface of the cancer cell and signaling it to reproduce.
Other antibodies carry tiny payloads of radioactive isotopes or poisons, which kill the tumor cell without affecting surrounding tissue. IDEC Pharmaceuticals in San Diego has just completed final rounds of testing on Zevalin, an antibody that is hooked to the radioactive isotope yttrium-90. Last month IDEC reported that the tumors in about one-third of 73 late-stage non-Hodgkins lymphoma patients were undetectable after being treated with Zevalin.
Antibodies are also being drafted to prod the immune system into attacking cancer cells. Clinicians have long dreamed of marshaling the body's own defenses to fight cancer, if only they could get the immune system to recognize cancer cells as easily as it spots foreign invaders such as bacteria and viruses. Researchers at Dendreon Corp. in Seattle have found a way to do just that by enlisting dendritic cells, some of the body's most potent immune stimulators.
Two years ago, Mohammad Omidian, 58, a general contractor from Orinda, Calif., had failed to respond to chemotherapy treatments for multiple myeloma that was eating away at his bones. He had shrunk 3 in. and was so weak, he says, "I could not sneeze without holding on to something." His doctors put him on Dendreon's experimental treatment Mylovenge, which required extracting dendritic cells from Omidian's blood, mixing them with molecules from myeloma cells and then returning them to the patient so they could deliver a swift kick to his immune system. Within two weeks, Omidian felt strong enough to return to work. Within two months, his cancer was in a remission that lasted until late last year, when he resumed treatment with Mylovenge.
Other companies are focused on boosting the immune system with vaccines that can direct it to target cancer cells. A new vaccine developed at Memorial Sloan-Kettering binds a protein from a mollusk called a limpet to seven different types of sugars and a protein fragment found only on cancer cells. The vaccine is then mixed with saponin, a soaplike derivative from a South American tree. This witch's brew serves to annoy the immune system, revving it up enough to attack cancer cells that are carrying the same sugars and protein fragment.
Such therapies will not, on their own, be able to rid the body of large tumors. So it is likely that oncologists will put together cocktails of treatments, each using a different strategy to outfox the cancer. In the future, the cell-killing drugs of traditional chemotherapy will be combined with treatments that aim simply to stop tumors from growing. The latter include the cox-2 inhibitors, drugs that are chemically related to pain-killers like ibuprofen and that appear to force cancer cells to self-destruct. Chemotherapy will also be used with so-called antiangiogenic factors, relatively nontoxic compounds that blunt the growth of new capillaries.
Tumors, it turns out, cannot grow much beyond the size of a peppercorn without an ever expanding network of blood vessels. Clinicians are testing more than a dozen treatments aimed at halting that process, including some old-line drugs that have turned out to have antiangiogenic properties. Thalidomide, which caused devastating birth defects in some 12,000 children worldwide before it was withdrawn in the early 1960s, is finding a new lease on life against multiple myeloma and liver cancers. Pharmaceutical giant Bristol-Myers Squibb is testing an antiangiogenic drug that was initially developed to keep cancer from worming its way into surrounding tissue. It's also investigating whether low, steady doses of traditional chemotherapy may be able to beat back blood vessels, a treatment that would have the added benefit of minimal side effects.
It's clearly too soon to declare victory in the war on cancer, since 9 out of 10 new treatments will fail clinical trials. But doctors who treat the disease are experiencing a surge of optimism the likes of which they have never felt before. "It's no longer spin the wheel, let's try this drug, maybe it will work," says Henry Friedman, a neuro-
oncologist at Duke University Medical Center. "We're going to know why a drug is or isn't working." And given the nature of cancer and the scientists who study it, if one approach doesn't fly, there will be no shortage of other ideas to try.
Mental Illness
Probing the Chemistry of The Brain
By FREDERIC GOLDEN
Asked once what makes people happy, Sigmund Freud replied, "Work and love." A strange answer from the man who invented the psychoanalyst's couch? Perhaps, but in his day, doctors could offer little more for patients suffering from anxiety or depression. And when faced with intractable mental illnesses like schizophrenia, they had to resort to brute force: inducing seizures and comas with chemicals and electric shocks, infecting patients with malaria to provoke brain-clearing fever, or slicing away parts of the brain's prefrontal cortex. In general, desperation guided treatment of the deranged.
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COVER STORY
Special Report: The Future of Medicine
With the mapping of the human genome the process by which new drugs are developed is being turned upside down. These drugs will also change our lives
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Rebel with a Cause
The real-lifestory of an anti-Mafia activist in Sicily makes for a handsome film with a political message
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