Epidermal growth factor inhibits colitis-associated cancer
Epidermal growth factor (EGF) is a protein that normally regulates intestinal healing. However, biological therapies such as EGF also may pose the risk of increasing the possibility of cancer.
Brent Polk, chair of the Department of Pediatrics at the Keck School of Medicine of USC, and Philip Dubé, both of The Saban Research Institute of Children’s Hospital Los Angeles, have demonstrated that in preclinical models, EGF encourages healing and provides powerful anti-inflammatory properties that prevent inflammation-induced cancer.
Crohn’s disease and ulcerative colitis, collectively known as IBD, are chronic debilitating conditions caused by inflammation to the intestinal tract. Together, these conditions affect as many as 1.4 million Americans and, like many other chronic diseases, this incidence is increasing every year in the developed world. Symptoms include persistent diarrhea, bleeding, abdominal pain, fatigue and weight loss. Lifelong inflammation in IBD significantly increases the risk for cancer development.
“Effective treatments for IBD have been limited by our lack of understanding of what causes these disorders, how to interrupt the inflammatory process and the long-term consequences of various treatments,” said Polk, who is also director of The Saban Research Institute and a professor of pediatrics and biochemistry and molecular biology at the Keck School. “An intriguing possibility is to build on the body’s own natural healing processes to induce healing and disrupt inflammation.”
EGF is a protein that normally regulates intestinal healing. A clinical trial, published in 2003, showed that EGF therapy might be extremely effective in patients with ulcerative colitis. However, this approach was highly criticized because EGF also has been associated with tumor development. Since EGF naturally promotes healing in the intestine, it has great potential as a therapeutic agent but any associated risk of cancer required clarification.
In order to determine the relationship between EGF and tumor development, the investigators blocked EGF and expected to also block colon tumor development. Surprisingly, they discovered that inactivating EGF resulted in increasingly severe colitis and dramatically increased colon tumor growth.
In a paper published online in The Journal of Clinical Investigation, the investigators reported that EGF encourages healing and provides powerful anti-inflammatory properties. Together, these functions actually prevent inflammation-induced cancer, superseding any potential tumor-promoting role.
“There is a great need for these new therapies, as current medicines and surgical options for IBD patients cause many debilitating side effects,” said Dubé, who is first author on the paper. “By building on the body’s natural healing system, we believe that we can develop therapies for IBD that are not only highly effective but, most importantly, safe.”