But better diagnostics will begin to make a real difference only when they’re coupled with more effective treatments, treatments that are fine-tuned to combat particular types of cancer. Even “if you can distinguish 50 different lymphomas,” says Yale University School of Medicine pathologist Michael Kashgarian, “what does it matter whether it’s type A or type Z if the therapy is the same?”
In this area of cancer drug discovery,DNA chips are also playing a key role. Just as the rapid analysis of a large number of genes is helping to profile cancer for better diagnostics, it is also providing valuable clues to how to attack cancer cells.
Researchers have long believed that developing new therapies would begin with finding cancer-associated genes, but the past two decades have been filled with disappointment. Stephen Friend, once an oncology researcher at the Whitehead Institute for Biomedical Research in Cambridge, MA, and now chief executive officer of Rosetta Inpharmatics in Seattle, blames what he calls the “my-favorite-gene approach.” Biomedical researchers would spend years tracking down one gene associated with a particular cancer, then proceed on the assumption that that gene, or the protein it coded for, would make a great target for new drugs. But, Friend says, “the chances were in 999 out of 1,000 cases that you’d be wrong.” Very few genes work alone and in such simple and direct relationships with the body to cause disease. “God, were we stupid!” he says.
Friend is now convinced that technologies such as DNA chips that allow researchers to find all the genes involved in a disease are the way to go. (Rosetta plays a role in such research by selling software and other services for reading microarrays.) Not only can DNA chips help identify all the potential drug targets for a given type of tumor, they can also help rule out the genes that are active in healthy tissues. That way, drugmakers can develop precisely targeted treatments that kill cancer cells without damaging other parts of the body.”Drugs,” says Friend, “are going to be developed at a tenth the cost and in a third of the time by improving targeting and making sure compounds don’t pick up unwanted side effects.”
Eos Biotechnology, a South San Francisco company that is developing new cancer therapies using DNA chips from its partner Affymetrix, is betting he’s right. In the company’s labs, vice president of genomics research David Mack holds up one of those chips, which contains virtually the entire set of human genes. “The ability to generate the human genome on a chip today is incredible,” he says. Eos uses the chips as a platform on which to compare genetic activity in normal human cells and, say, a breast-cancer cell. Computers can then sort out the genes that are active only in the diseased cell.Moreover, they can select just those genes that present the best targets for drugs.
Under the traditional drug-development paradigm, once researchers identify a set of potential targets, they begin to stumble ahead into animal and human trials, with educated guesses about which potential drugs might be effective against a given target, and which of those drug candidates might have toxic side effects.Very often, it’s only much later in the process that a candidate’s problems become apparent-at a huge cost in time and money.
By contrast, Eos continues to use microarrays and other high-volume genomic techniques to test the drugs, better predicting which will be the most effective and the least toxic before more costly testing even begins.According to Mack,”We’re seeing data-driven science now, which hasn’t been the previous paradigm.”Thanks in part to the use of DNA chips, the company plans in the coming year to begin clinical testing of its first drug-which attacks a tumor’s ability to generate its own lifesustaining blood supply-with more than a dozen other anticancer drugs expected to follow rapidly. “The promise of these technologies to impact patients is here-finally,” he says.
While DNA chips have only been around for five years or so, they have already helped to get a number of new drugs into pharmaceutical-company pipelines, and to identify many potential new drug targets and sources of earlier diagnosis.With these advances, it is likely that cancer therapy will become both more complex and more effective over the next decade. Eventually, each patient’s cancer fingerprint will be met with just the right drug “cocktail,”or combination of therapies. Doctors will have new tools to diagnose and treat cancers much earlier-when the chances of cure are far better-and to monitor a patient’s progress, ensuring that tumors don’t develop resistance to the treatment.
It may take more than a decade before such practices become the norm, but if and when they do, they will change everything for people like John Leventhal.His (mis)diagnosis of lung cancer came when he was the age at which his own father got news of the cancer that eventually killed him-a fact that ratcheted up Leventhal’s terror when he learned he might have cancer. But should his children ever find themselves in the same shoes, perhaps they won’t have nearly as much to fear.