WILMINGTON, DE — Colorectal cancer, long thought to begin when cells start growing out of control, may instead take root when the body’s normal tissue renewal quietly slows to a crawl, according to new research from scientists at ChristianaCare and the University of Delaware.
The study, published in the journal Cancers, identifies a critical early breakdown caused by mutations in the APC gene, a defect found in roughly 90 percent of colorectal cancers. Rather than accelerating cell growth, researchers found the mutation disrupts the colon’s tightly regulated renewal cycle, causing immature cells to pile up, tissue structure to distort, and early tumors to form.
“This finding changes how we think about the very first steps of colon cancer,” said Bruce Boman, M.D., Ph.D., senior author of the study and a senior researcher at the Cawley Center for Translational Cancer Research at ChristianaCare’s Helen F. Graham Cancer Center & Research Institute. “Instead of cancer starting because cells grow too fast, we found that it may start because the normal tissue renewal process slows down.”
Under healthy conditions, the lining of the colon renews itself continuously. Billions of cells are shed and replaced as new cells form at the base of microscopic structures called crypts, mature as they move upward, and are eventually discarded. That orderly flow keeps the tissue functional and stable.
The new research shows how that system falters when the APC gene is mutated. The mutation creates a bottleneck in the renewal cycle, trapping dividing cells that should have matured and moved on. Over time, that cellular “traffic jam” leads to the formation of adenomas, early growths that can become malignant.
To document the process, the team compared healthy colon tissue with tissue from patients with familial adenomatous polyposis, an inherited condition driven by APC mutations. Mutant tissue showed a clear pattern: an overabundance of immature, rapidly dividing cells; fewer fully developed cells; an expanded zone of cell division; and a prolonged renewal cycle.
Researchers paired these tissue findings with advanced computer modeling that simulates how colon cells grow and migrate. When the model’s renewal process was artificially slowed, it reproduced the same crowded, distorted tissue architecture and early tumor-like growths seen in patient samples.
The work builds on earlier ChristianaCare and University of Delaware studies that identified the basic biological rules governing healthy colon renewal. By showing what happens when those rules are disrupted, the researchers say they have uncovered a critical window when cancer may begin long before visible tumors appear.
Colorectal cancer remains one of the most common and deadly cancers worldwide. According to the World Health Organization, about 1.9 million people are diagnosed each year, and roughly 930,000 die from the disease annually.
The findings could also reshape future prevention and treatment strategies. By restoring proper timing to the renewal process, researchers suggest it may be possible to halt or slow tumor formation before cancer becomes established.
“This study shows that cancer isn’t just about rogue cells,” Boman said. “It’s about a system that’s fallen out of rhythm. If we can reset that process, we may be able to intervene much earlier than we ever thought possible.”
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