Lynch syndrome is an inherited condition that greatly increases the risk for intestinal cancer. In this image, the drug rapamycin has eliminated differentiated tumor cells from the small intestine of a Lynch syndrome mouse model, but two types of cancer stem cells have resisted rapamycin: Lgr5+ (green) and Bmil+ (purple) stem cells. (Also visible are Lgr5+ stem cell–associated Paneth cells, in red.)
Tumors return when rapamycin therapy is stopped—and Lgr5+ cells, in particular, are suspected of regenerating tumors. Winfried Edelmann, Ph.D., and colleagues are studying a drug that makes Lgr5+ cells sensitive to rapamycin by inhibiting the membrane protein MDR1 (multi-drug resistance 1), which pumps out rapamycin and other anticancer drugs. Dr. Edelmann is a professor of cell biology and of genetics and the Joseph and Gertrud Buchler Chair in Transgenic Medicine at Einstein.