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A simple pill to treat cancer sounds too good to be true. But striking results with the drug known as STI-571, or Gleevec, have shown how effective a custom- designed cancer drug can be. And Gleevec is only one of many such agents now under development.

This new generation of cancer fighters, as it emerges, will be the long-awaited payoff from decades of research into the molecular biology of cancer. Unlike chemotherapy and radiation, blunderbuss weapons that attack healthy as well as cancerous cells and can cause severe side effects, the new agents are designed to kill cancer cells alone. In principle, they should eliminate malignancies more effectively while being far gentler on the patient.

Until Gleevec, progress in developing the new agents had been slow and generally unspectacular. Researchers and drug companies have put enormous effort into developing drugs against some obvious targets in cancer cells, such as a frequently errant signaling protein known as ras, but so far without much success. Herceptin, one of the first rationally designed cancer drugs to reach the market, is useful in certain cases of breast cancer but is no panacea.

Gleevec seems to be a smash hit, although so far it has been proved to work only on two comparatively rare cancers, and experts caution it has been in use far too short a time to be fully confident of its longer term usefulness. Taken as a pill, the drug has put into remission 90 percent of patients in the early stages of chronic myelogenous leukemia, one of the four kinds of leukemia. It has also secured speedy remissions in some 60 percent of patients with a rare and otherwise deadly stomach cancer known as gastrointestinal stromal tumor. The drug was approved by the Food and Drug Administration last month.

"This is really a fantastic breakthrough for patients suffering from chronic myelogenous leukemia, but it is also a validation of the idea that if we understand targets we can develop useful drugs," said Dr. Frank McCormick, director of the cancer center at the University of California at San Francisco.

Dr. Harold Varmus, president of Memorial Sloan-Kettering Cancer Center, described the Gleevec results as "an incredibly important proof of principle because it shows the public that this investment can lead to drugs that really do work the way people have been hoping for 20 to 30 years."

Biologists believe that after some initial mutation in a gene, a growing clone of misbehaving cells acquires one mutated gene after another until each of the cell's cancer defenses has been compromised. That understanding has made clear what goes awry in cancer cells but also pointed to how hard it might be to take down a cell that has sabotaged all natural restraints on its growth.

For example, the initial damage that leads to chronic myelogenous leukemia occurs in a gene that makes a signaling protein called abl. The errant abl protein is hyperactive and seems to be a major driver of the cancer. But the white blood cells are highly likely to acquire damage in additional genes before they can start to proliferate as leukemic cells, said Dr. Robert A. Weinberg, a cancer expert at the Whitehead Institute for Biomedical Research in Cambridge, Mass.

Gleevec is a small chemical designed to slip into and jam signaling proteins like abl. An astonishing feature of Gleevec's success is that the cancerous cells pack up and die even though the drug's role is just to shut down their signaling proteins. It seems they have become so dependent on the hyperactive signaling pathway that its loss is a lethal blow.

Dr. Varmus said the Gleevec trials and similar results from mouse experiments suggested that turning off a hyperactive signaling protein could be a general way of forcing cancer cells to trigger the self-destruct mechanism all cells possess. This could mean the downstream signaling proteins, as well as the hyperactive protein that helped cause the cancer, could be suitable targets for drugs, he said.

From the decoding of the human genome, it is known that as many as one-fifth of all human genes make proteins that are involved in signaling. A special subset of these proteins, known to biologists as tyrosine kinases, are particularly prone to go awry and show up in hyperactive form in many human cancers. There are about 90 kinds of tyrosine kinases, of which 58 are embedded in the cell's outer membrane. Called receptors, the proteins pick up messages received from hormones and generate a corresponding signal inside the cell. The other 32 tyrosine kinases work in the cell's interior, relaying messages to the nucleus.

Gleevec was originally designed to inhibit a receptor kinase called PDGFR-beta, which is hyperactive in glioma, a brain cancer. But it also turned out to inhibit another kinase receptor called c-kit, which is overexpressed in gastrointestinal stromal cancer, as well as abl, the internal kinase whose gene goes awry in chronic myelogenous leukemia.

Some 30 of the 58 kinds of receptor tyrosine kinase are known to run amok in various kinds of human cancer, as are 15 of the internal kinases, according to a list drawn up by Peter Blume-Jensen and Tony Hunter of the Salk Institute in San Diego and published in the current issue of Nature.

All of these proteins are in principle suitable targets for small molecule drugs, and the receptors can also be targets for antibodies. Herceptin, a drug already approved, is an antibody that aims at Her2/Neu, a tyrosine kinase receptor whose gene is amplified in 25 percent to 30 percent of cases of metastatic breast cancer.

Several companies are developing Gleevec-type drugs against other important receptors. AstraZeneca's Iressa, now in Phase 3 trials, the final test before possible F.D.A. approval, hits the epidermal growth factor receptor that is active in non- small cell lung cancer. Novartis, the company that developed Gleevec, is also working with drugs that inhibit the epidermal growth factor receptor and the vascular epithelial growth factor receptor. Some of these inhibiting drugs have a significant but minor effect on tumors, so large and expensive clinical trials are required to demonstrate their effectiveness. Still, as more such agents are developed, "it's the beginning of more rational therapy," said Dr. Gregory Burke, global head of development for Novartis's oncology unit.

The protein kinases are an especially suitable target for cancer drugs because they become more active in malignant cells and can be shut down with inhibitory drugs. But aberrant signaling proteins are just one class of misbehaving components in a cancer cell. Another is a group of substances that control the cell's division cycle, chief of which is a protein called Rb. Rb's role is to block a cell from dividing unless it is in good genetic shape, which cancer cells are not. All cancer cells must therefore knock out their Rb.