Magazine

Introduction


At the American Association for Cancer Research's annual meeting in New Orleans on Mar. 24-28, some 14,000 attendees discussed the latest lab discoveries. Much of the excitement involved newly found genetic clues, but studies also covered everything from the foods we eat to drug breakthroughs. Senior Writer Catherine Arnst reports on some highlights: One of the tragic aspects of tobacco is that decades after quitting, smokers still suffer from its poisonous effects. Half of newly diagnosed cases of lung cancer occur in former smokers. Now, researchers at M.D. Anderson Cancer Center in Houston have found that a synthetic vitamin A compound may repair some damage in the lungs of former smokers, providing some protection from cancer. The compound reduces the activity of telomerase, an enzyme that enables cancer cells to live indefinitely, giving them time to multiply and turn malignant.

Earlier studies had shown that vitamin A compounds known as retinoids can prevent cancer. To find out why, the Anderson researchers studied 57 former very heavy smokers with no signs of lung cancer. The vitamin A analog was administered to 27, while the other 30 received a placebo. Both groups had similarly high levels of telomerase in their lungs at the start of the study. But after six months, the group receiving vitamin A experienced a sharp drop in telomerase levels. The levels in the placebo group rose slightly. Agents that prevent cancer are notoriously diffcult to assess without waiting years to see if cancer develops. The researchers, led by Dr. Li Mao, said they were encouraged both by the impact of vitamin A and the clear early results. As the war against cancer focuses on ever more specific molecular targets, knowledge about the structure of cells becomes increasingly important. Two discoveries concerning basic structures in human cells were reported at the AACR meeting. They suggest new opportunities for developing drugs to block tumor growth, researchers said.

One involves knots in DNA that are created when DNA folds over on itself. Scientists from Cyternex Inc. in Del Mar, Calif., reported that one of these knots, or quadruplexes, seems to regulate the c-myc gene, a cancer gene that helps extend the lives of tumor cells. Laurence H. Hurley of the University of Arizona, working with Cyternex, says his team has developed compounds that help this quadruplex form and then stabilize, thus turning off the c-myc gene. He hopes to begin clinical trials in 2002.

Meanwhile, scientists at Amgen Corp. have deciphered the three-dimensional structure of a human protein that plays a critical role in the growth and survival of most tumor cells. The protein is an insulin-like growth factor receptor called IGF-1R. Amgen researcher Xiaotian Zhu says his team has made the first detailed molecular map of IGF-1R, giving researchers the information they need to develop small molecules to block it. If you're worried about prostate cancer, it might pay to eat an apple a day. Or an onion. Researchers at the Mayo Clinic in Rochester, Minn., report that a natural substance called quercetin significantly reduced the ability of prostate tumor cells to absorb the hormone they need to develop and proliferate. Quercetin is found in apples, onions, leafy vegetables, green and black tea, beans, and red wine.

The team, led by Dr. Nianzeng Xing, cautioned that the study has been done only on cancer cells cultivated in the lab, and quercetin hasn't been tested in human patients. But it has two advantages as a potential treatment: It is abundant and safe. Prostate cancer, the most common cancer in men, will strike 198,100 Americans this year and kill 31,500, according to the American Cancer Society. Existing treatments have severe side effects, so scientists have been searching for a safer one.

The researchers found that quercetin reduced prostate cells' absorption of androgens, the male hormones that stimulate prostate cancer. Next, the Mayo team will test quercetin in mice that have been bioengineered to develop prostate cancer. Publication of the human genome sequence this year led to predictions that many diseases could be eliminated by manipulating a patient's genetic makeup. That's years in the future. But in the near term, genetic testing may help doctors better tailor existing treatments.

Researchers are finding that changes in an individual's genetic makeup affect how a tumor responds to treatment. "A pretreatment blood test could determine what dose of drugs or drug combination would be most effective for an individual patient," says Howard L. McLeod of Washington University School of Medicine.

In one study, a team from Duke University and privately held DNA Sciences Inc. found that women with two specific genetic variations survived breast cancer half as long as those without the variations. A third variation protected against cancer--those patients survived twice as long as women without the variation. Tests for these variations could help doctors treat patients' cancers more effectively.

In a separate study, researchers at the University of Aberdeen in Scotland found a mutation that reduces the production of P-glycoprotein (PGP), which pumps chemotherapy drugs out of tumor cells before they can kill them. The next step will be to see if differences in PGP production do indeed lead to different patient responses to treatment.


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