Targeting Colon Cancer Plasticity May Prevent Drug Resistance

Scientists in Germany have discovered that colon cancers contain two different cell types, characterized by mitogen-activated protein kinase (MAPK) and NOTCH signaling, respectively, which can regenerate each other when one type is killed by a targeted therapeutic. The studies, headed by David Horst, Ph.D., at the Charité University Hospital in Berlin, suggest that this cell plasticity allows the tumor to sidestep drugs directed against one or other of the two signaling pathways, and that combination strategies for treating colorectal cancer may improve patient outcomes. Early tests in mice confirmed that a combination of NOTCH and MAPK inhibitors more effectively blocked cancer growth and improved survival than treatment using only one or the other type of targeted therapeutic. 

“…when combining both therapies to target both cell populations, we found strong repressive effects on tumor cell proliferation and increased cell death, resulting in slower tumor growth and prolonged survival ...