Christiana Care discovery holds promise of changing course of colon cancer treatment

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Christiana Care discovery could change nature of colon cancer treatment

In a discovery that may have significant impact on the future of colon cancer treatment and research, scientists at the Helen F. Graham Cancer & Research Institute’s Center for Translational Cancer Research  at Christiana Care Health System have defined a  signaling pathway that regulates colon cancer growth. 

The study, led by Senior Research Scientist Bruce Boman, M.D., Ph.D,  was  reported in the October 5 issue of  Oncotarget.

“Our findings point to a number of possibilities for developing more effective stem cell targeting therapies for advanced colorectal cancer,” Boman said.

Conventional research over the last 50 years has been guided by the idea that tumors undergo a series of genetic mutations that lead to the unchecked growth of tumors and their progression to metastatic cancer. Traditional therapies designed to kill the bulk of cancer tumor cells continue to fall short of a cure for advanced, drug-resistant colon cancers.

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“Our thinking has shifted to the insight that cancers originate in tissue stem cells through dysregulation or malfunction of the self-renewal process, and that cancer stem cells drive tumor growth,” he said. “It follows that the optimal way to treat cancer (especially advanced cancer) is to eliminate cancer stem cells.”

Tumors develop when certain mutations or mistakes occur in the genes of normal tissue cells that regulate stem cell renewal and population size. 

“We discovered that the retinoic acid or RA signaling pathway acts to induce differentiation of colon cancer stem cells and reduce cancer stem cell overpopulation, which puts the brakes on the primary mechanism that drives colon cancer development,” Boman explained. 

Previous studies in Dr. Boman’s lab pinpointed aldehyde dehydrogenase (ALDH) as a biomarker for normal and malignant human colon stem cells and showed that ALDH tracks stem cell overpopulation during the formation of colon tumors. 

Because ALDH is both a marker for stem cells in many tissues and a key enzyme in retinoid acid signaling, Dr. Boman’s research team at the Graham Cancer Center pursued further study of the retinoid signaling pathway in normal and malignant colonic stem cells. 

Based on the  findings, the investigators concluded that retinoic acid signaling provides a mechanism to selectively target colon cancer stem cells and reduce the self-renewal ability of those stem cells during cancer development.

Their findings suggest treatment with retinoid drugs, which are derived from vitamin A, could provide a therapeutic strategy to selectively target cancer stem cells and decrease the number of highly resistant cancer cells. 

Colorectal cancer is the second leading cause of cancer-related deaths in the United States, equally affecting both men and women.

 

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