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Other substances in the works may be further from the market, but they are in some ways even more exciting. Several of them take aim at a growth-signaling protein made by a gene called RAS (for rat sarcoma, the cancer in which it was first discovered). In about 30% of cancers, the RAS protein is stuck in an "on" position, mindlessly ordering the cell to divide again and again. It plays a role in 90% of pancreatic cancers, 50% of colon cancers and 25% of lung cancers. Dr. Edward Scolnick discovered the RAS gene in rats while working at the National Cancer Institute in 1978. Now president of Merck Research Laboratories, he is overseeing the development of a drug that stops the RAS protein from sending its malignant message. Several other big drug companies, including Bristol-Myers Squibb, Johnson & Johnson and Schering-Plough, are testing similar drugs. "We think the odds are that if you treat people with a good RAS drug, you will produce some clinical benefit," says Scolnick. Finding a new kind of cancer therapy based on gene discoveries like his own is, Scolnick admits, "my fondest hope."
Other drug companies are targeting another common cancer gene: one that codes for a protein called the EGF (epidermal growth factor) receptor. This receptor, which takes in growth signals and relays them to the RAS protein, is found in abnormally high numbers on the surface of about 40% of tumor cells, including about 90% of lung-cancer tumors, some prostate tumors and other malignancies. Researchers at M.D. Anderson Cancer Center in Houston are testing an antibody to EGF receptors in patients with advanced head and neck cancers. But most other groups, including teams at drug makers Pfizer, Novartis and Zeneca, are using smaller molecules that, unlike antibodies, could ultimately be taken orally. "We have a very exciting tablet that is taken once a day," says Dr. George Blackledge, head of new cancer projects at the Zeneca Group. Testing on patients is still at a very early stage. "We have to be cautious," he says, "but potentially this could be an effective new treatment for the most common type of lung cancer."
At the Memorial Sloan-Kettering Cancer Center in New York City, Dr. Mark Malkin is working with a substance that targets a receptor for another growth factor called PDGF (platelet-derived growth factor). This receptor studs the surfaces of cells in certain ovarian, prostate, lung and brain tumors. Malkin has been testing the drug, SU101, on patients with an extraordinarily deadly brain tumor called glioblastoma. Median survival for a patient found to have this cancer is 14 months.
So far, the drug, manufactured by Sugen, appears to slow or arrest tumor growth in about a third of glioblastoma patients, but it's too soon to say how long the benefits will last. Side effects appear to be mild. "We have one patient who's been on it for two years and three months," says Malkin. "His tumor is still there, but it's stable. He's alive; he's at work. For someone with recurrent glioblastoma, that's remarkable."