Cetuximab, marketed as Erbitux©, is one of the key therapies for metastatic colorectal cancer. Yet the cancer still returns in some patients, shortening overall survival. An MD Anderson study published in the Journal of Clinical Investigation may help explain why the body sometimes becomes resistant to this therapy.
"We investigated the role of extracellular methylation in EGFR signaling and unexpectedly discovered new information about how EGFR renders cancer cells resistant to cetuximab antibody therapy," says Mien-Chie Hung, Ph.D., chair of Molecular and Cellular Oncology.
Methylation is a process by which proteins are chemically altered. When expressed aberrantly, EGFR can lead to runaway cell growth, reduced cell death, tumor formation and metastasis. Hung's group found that expression of methylation-defective EGFR reduced tumor growth in mice.
The study was funded by the National Institutes of Health; the Cancer Prevention and Research Institute of Texas; The University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund; the Ministry of Science and Technology, International Research-Intensive Centers of Excellence in Taiwan; China Medical University Hospital Cancer Research Center of Excellence; the Center for Biological Pathways; the American Cancer Society; and the King Abdullah University of Science and Technology.