Biologists at the University of Houston have contributed to a potential breakthrough in Crohn’s disease treatment by shifting clinical focus from symptom management to addressing the disease’s primary underlying causes.
Crohn’s disease is a chronic inflammatory bowel disease that affects approximately 1 million Americans and involves a cycle in which the immune system attacks the epithelial layer and disrupts the “gut barrier.” When this lining becomes damaged and unable to repair itself, the barrier is lost and bacteria and toxins can leak into the body, promoting chronic inflammation and disease progression.
Anti-inflammatory drugs are the standard of treatment for disease flare-ups or flare-ups, but only about 20% of patients achieve durable remission with these traditional methods.
In a new study published in Progress of gastric hepResearchers from the University of California, Baylor College of Medicine, and the University of Texas MD Anderson Cancer Center have proposed a new idea that the disease is caused by an inherent defect in the epithelial lining that also promotes an immune response. By repurposing two existing anti-cancer drugs, the research team aims to stop the inflammatory cycle triggered by epithelial cells and allow the intestinal barrier to repair itself.
This is a paradigm shift in the way we think about this disease. Because the cause of the disease is unknown, existing treatments primarily manage symptoms. We believe our research will bring us closer to identifying those factors. ”
Seema Khurana, senior author, Moore Professor of Biology and Biochemistry, University of California
Target stress signals
Dr. Khurana has been a leading researcher in gastroenterology for nearly 30 years. Her team’s 2018 study linked intestinal barrier health to the progression of Crohn’s disease for the first time, noting that under chronic stress, Crohn’s disease patients’ intestines begin to kill their own epithelial cells rather than regenerate.
In the new study, the team found that this dysfunction of epithelial cells promotes disease progression by actively inhibiting epithelial regeneration.
“In healthy cells, stress signals go up and when the stress is relieved, the signals go down. In patients with Crohn’s disease, this stress signal is always on,” Khurana said. “When stress signals are constantly turned on, cells are unable to cope with stress and undergo a type of programmed cell death called necroptosis, which leads to further inflammation.”
The research team determined that using low concentrations of the two cancer drugs may be key to solving this problem. Pazopanib and ponatinib were found to inhibit early cellular stress response signaling and cell death, promoting natural repair and regeneration of the intestinal lining.
Focus on the pathway to patient care
Repurposing existing medicines offers significant advantages in medical development. Using drugs already approved by the U.S. Food and Drug Administration reduces the risk of clinical trial failure and largely avoids the high costs and decade-long timelines associated with new drug discovery.
The study also used patient-derived organoids (“mini-organs” grown from actual patient tissue), the gold standard in modern biological research. This approach ensures that the results are highly relevant to human biology, paving the way for future clinical applications.
“If we had to start from scratch to identify and develop a drug, it could take 10 to 15 years and cost $1 billion to $2 billion,” Khurana said. “Patients suffering from chronic Crohn’s disease are seeking immediate relief. Our goal was to make our findings more applicable to real patients.”
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Reference magazines:
Halder, D. Others. (2026). Integrated stress responses and necroptosis drive epithelial dysfunction in Crohn’s disease: Repurposing anticancer drugs to heal the permeability barrier. Progress of gastric hep. DOI: 10.1016/j.gastha.2026.100950. https://www.ghadvances.org/article/S2772-5723(26)00071-3/fulltext
