Research by Irving Coy Allen Paves Way for Future Colorectal Cancer Treatments

A recently published paper on a kinase and its importance in triggering cellular responses caps more than 12 years of research.

Research led by Irving Coy Allen at the Virginia-Maryland College of Veterinary Medicine has uncovered a potential pathway for future treatments of colorectal cancer in humans. A paper published in May in the American Gastroenterological Association journal, Cellular and Molecular Gastroenterology and Hepatology, highlights the critical role of NF-kB-inducing kinase (NIK) in triggering cellular responses that mitigate the risk of colorectal cancer development.

"The gene itself is colloquially called NIK, and it encodes a protein that is a kinase, which means it basically turns on or turns off -- mostly turns on -- lots of different genes and pathways," explained Allen, a professor of inflammatory diseases in the Department of Biomedical Sciences and Pathology. "It gives us a central spoke in a hub of biological mechanisms that can be targeted with possible therapeutics. We do know that there are companies working on developing drugs to target NIK. We're hoping that this can provide them with incentive to go after these drug candidates more aggressively."

Colorectal cancer is the second deadliest form of cancer in the United States, claiming over 52,000 lives in 2023. Current treatments, primarily chemotherapy, can be harsh and challenging for patients to endure.

"By identifying new markers and new drug targets, it may provide us with better therapeutic approaches that can minimize side effects and improve overall patient outcomes," Allen said.

The study predominantly utilized mice for its research, which alone offered significant insights. However, Allen's team extended their research to human patients to ensure the relevance of their findings.

"By modeling it in mice, we were able to identify things to look for in humans," Allen stated. "Through collaboration with the Duke University Medical Center and colleagues here at the Virginia Tech Carilion School of Medicine, we were able to get human specimens to confirm that what we were observing in the mouse models was also true in human colorectal cancer patients."

The future medical applications of these findings will unfold as researchers pursue treatments targeting NIK and its interactions with other proteins.

"Our study identified changes in a significant signaling pathway in human patients," Allen said. "That presents a variety of possible targets that have not been previously evaluated in that pathway where you could potentially design therapeutics."

The publication marks the culmination of an extensive research journey for Allen. Graduate students Kristin Eden '06, DVM '10, Ph.D. '18; Holly Morrison Ph.D. '23; and Brie Trusiano Ph.D. '24 played pivotal roles in advancing the research.

"When I first came here 12 years ago, my postdoctorate work had identified some hints that this pathway might be important in the context of colorectal cancer and also in the context of inflammatory bowel disease," Allen recalled. "Completion of this work has been very satisfying, knowing that it helped to launch the careers of these three talented graduate students and several undergraduate researchers as well."

With his studies on the NIK pathway in colorectal cancer now concluded, Allen and his team will shift focus to other cancers influenced by NIK and its signaling pathways. However, Allen hopes others will build on these findings to develop life-saving treatments for colorectal cancer.