Clues gleaned from studying inflammatory diseases like Crohn’s disease (colon) and Chronic Obstructive Pulmonary Disease (lung) may help scientists discover new ways to treat cancer.
Internationally renowned stem cell expert Frank McKeon was recruited in 2015 to direct the University of Houston Somatic Stem Cell Center, with the help of a Recruitment of Established Investigator Award from CPRIT. He was a senior group leader at the Genome Institute of Singapore, after 23 years as a professor at Harvard Medical School.
McKeon has cloned stem cells from patients with Crohn’s disease and COPD, and found that there are “rogue” populations of stem cells that cause the debilitating and chronic symptoms. But these stem cells, which release substances that cause the immune system to go out of whack, exist alongside populations of normal stem cells.
Now that McKeon can grow these patient-matched stem cells—normal and abnormal—together in a laboratory culture, he can test drugs to find out which ones kill the bad cells while allowing the normal ones to survive and flourish.
Approximately 15% of patients with inflammatory bowel disease eventually die from an unusual colorectal cancer, McKeon says. And smokers who develop COPD are two or three times more likely to develop lung cancer than those who only smoke.
McKeon says it is probably the rogue stem cells that are the precursors to the unusual cancers. He is studying the relationship between the inflammatory stem cells and the development of cancer.
Another cancer that develops from a non-cancerous precursor is Barrett’s esophagus. This is a condition, thought to arise from chronic reflux, in which intestine-like cells occupy the lower esophagus.
McKeon is culturing stem cells of both normal esophagus and those that give rise to Barrett’s esophagus to figure out how to destroy Barrett’s cells before they ever turn into a deadly cancer. As many as 3 million Americans suffer from Barrett’s esophagus, and only a fraction of those will develop cancer. But for those who do, it is a deadly, incurable disease. Patients may develop Barrett’s esophagus as much as 20 years before esophageal cancer arises.
Using the stem cell cultures, McKeon is testing libraries of thousands of potential therapies.
“Our goal is to have a drug that can kill this pre-cancerous lesion independent of its risk of becoming a cancer,” McKeon says. “We very much want to have drugs that will do that, and we think we’ve already got them.”
McKeon works closely with his wife, Wa Xian, a professor and CPRIT Scholar at the University of Texas Health Science Center at Houston. McKeon credits his partnership with Xian, and the support of CPRIT, for the tremendous progress they have made since coming to Texas. “It’s gone much faster than I’ve ever imagined,” he said, “because even though we are at different institutions, everything we do is together.”
The couple is also investigating other cancers, like gastric, pancreatic, and ovarian.
McKeon received his undergraduate training in biology at Pomona College, and his Ph.D. in biochemistry and biophysics from the University of California, San Francisco. He joined the faculty at Harvard Medical School in 1986. He moved to the Genome Institute of Singapore in 2008 and has founded several startup companies to move this work toward novel therapies for patients.
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