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Dr. Stacy Norton was only 7 years old when her mother died of colon cancer, one of several family members struck by aggressive tumors at unusually young ages. Decades later, Norton rolled up her sleeve to help test if a new kind of vaccine might protect her and her own children from cancer.
The Houston doctor is among an estimated 1 million Americans who have Lynch syndrome, a faulty gene passed from a parent that puts them at extremely high risk of colorectal cancer and more vulnerable to certain other cancers, too. They're often urged to get yearly colonoscopies -- far more often than usual -- that can spot and remove precancerous growths called polyps.
Now scientists are creating vaccines that aim to go further, teaching the immune system to intercept this type of brewing colon cancer before it turns into a full-fledged tumor. At least three potential Lynch syndrome vaccines are in development, including two in early clinical trials in the U.S. and a third beginning in Britain.
The shot that Norton helped test appears promising enough that its lead researcher, Dr. Eduardo Vilar-Sanchez of the MD Anderson Cancer Center, expects a larger study to begin early next year.
"It gives me hope," said Norton, 59, of Houston Methodist Willowbrook Hospital. She had already survived a different Lynch-caused cancer and has two children in their 20s who inherited her mutation. If a vaccine pans out, "perhaps they won't have to have a colonoscopy every single year for the rest of their lives."
Everyone has what are called mismatch-repair genes, which are essentially spellcheckers to help fix DNA mistakes that can occur when our cells multiply. With Lynch syndrome, one of those genes can't do its job properly, making it harder for the body to stop a buildup of abnormalities that can lead to tumors, often before age 50.
Colorectal cancer is the most common consequence. The average person has a 5% risk of developing it during their lifetime. A Lynch carrier's risk can reach as high as 80% depending on which faulty gene they inherit, Vilar-Sanchez said.
Another big risk is endometrial, or uterine, cancer. Lynch carriers also are more likely to get other cancers including pancreatic, stomach, ovarian and certain skin cancers -- and a kind of brain tumor that killed Norton's sister at age 25.
Today there are two cancer-preventing vaccines, the HPV and hepatitis B shots that block infection from those tumor-causing viruses. But developing vaccines to prevent gene-caused cancer is more challenging than alerting the body to foreign intruders like a virus.
Lynch-fueled growths "tend to accumulate hundreds of mutations that are going to generate proteins that are novel, not made by our normal cells," Vilar-Sanchez said. "You can train the immune system to recognize those proteins."
In a first-step study, Norton and 44 other Lynch carriers tested a vaccine made by Swiss biotech Nouscom that teaches the immune system to spot 209 of those abnormalities in Lynch-caused precancers. That revved up tumor-eliminating T cells and a year later, colonoscopies showed fewer precancerous growths and no advanced polyps, the MD Anderson team reported in Nature Medicine.