This continues the thoughts we started yesterday on treating cancer.
"Fueling cancer
Still, this notion might have stalled without two other developments.
* First, epidemiological studies began to find links between cancer and the insulin-IGF axis in people.
* Then, the entire field of cancer treatment underwent a transformation.
"What got people's attention was the epidemiologic data," says Doug Yee of the University of Minnesota Cancer Center in Minneapolis. In 1998, researchers reported in the journal Science that the risk of prostate cancer among men with the highest circulating levels of IGF-1 was four times as great as the risk among men with the lowest IGF-1 levels. Similar findings quickly followed in breast, colon, and other cancers.
So far, colon cancer has the most consistent association with insulin and IGF-1 levels, says Edward Giovannucci of the Harvard School of Public Health, a coauthor of the 1998 Science study. In 1999, he and his colleagues reported that colon cancer rates were more than twice as high among men who had the highest levels of IGF-1 as they were among men with the lowest IGF-1 levels.
Such findings fit with global patterns of the disease. "If you look at the rates of colon cancer across the world, populations where you expect people to have low insulin invariably have low rates of colon cancer," Giovannucci says. Physical activity and reduced calorie intake can lower insulin levels; populations with more sedentary jobs and calorie-dense diets have higher rates of obesity and higher insulin levels.
"Once you become economically developed, colon cancer rates go up," Giovannucci says. Also, the risks for colon cancer read largely like a list of red flags for type 2 diabetes. Diabetes itself is a risk factor for colon cancer.
Scientists are quick to point out that a higher insulin level isn't the only chemical change that can occur with obesity. Levels of hormones that cause inflammation also rise, as do sex hormones, which can be produced in fat tissue. These and other changes in the body could themselves drive cancer. Or all these fluctuations could work in concert to feed malignancies.
 And it might be not only the IGF-1 of middle age that matters, but also the IGF-1 production that orchestrates development early in life. Studies have suggested that babies born at the highest birth weights—and children experiencing early growth spurts—have a greater risk of cancer as adults.
While epidemiologists gathered evidence for a relationship between insulin and cancer, a second, unrelated advance gave the insulin-cancer connection new life: treatment success using antibodies that can attach to precise targets. Antibody-based drugs are large molecules that take the parking space so its rightful owner can't use it. Herceptin, an antibody-based breast cancer treatment, came on the market in 1998, followed by others. Targeted antibodies were suddenly more than theory.
"I think once people got more comfortable making these drugs, the floodgates opened," says Yee. And when pharmaceutical companies started casting for other promising targets for antibody development, the IGF-1 receptor suddenly looked attractive.
"They turned around and said, 'You know, there's this IGF receptor,'" says LeRoith of Mount Sinai. Drug development didn't happen, and perhaps couldn't have, until epidemiology and the technology caught up with the laboratory evidence. "Labels: anti-aging, cancer, health, obesity |
