A study co-led by University of Texas at Dallas bioengineers identified a distinctive feature of tissues from young patients diagnosed with colorectal cancer, a disease that typically affects older patients.
Researchers found that both cancerous and noncancerous colon tissue was mechanically stiffer in younger patients with respect to older patients diagnosed with colorectal cancer. The findings, published in the Jan. 30 print edition of Advanced Science , suggest that stiffness may create an environment that promotes the development of colorectal cancer in people under the age of 50. This work may offer new approaches for preventing and treating this disease — known as early-onset colorectal cancer — a condition that has been mysteriously rising over the past 30 years.
“This is the first study to highlight the key role of biomechanical forces in the pathogenesis of early-onset colorectal cancer,” said Dr. Jacopo Ferruzzi , assistant professor of bioengineering in the Erik Jonsson School of Engineering and Computer Science and a corresponding author of the study. The UT Dallas researchers collaborated on the study with researchers from UT Southwestern Medical Center (UTSW).
“We consider this study a significant advancement toward identifying those at risk of early-onset colorectal cancer and finding new ways to treat them,” said co-corresponding author Dr. Emina H. Huang , executive vice chair of research for surgery at UTSW. She is a professor of surgery and of biomedical engineering and specializes in colorectal cancer in the Harold C. Simmons Comprehensive Cancer Center.
Early-onset colorectal cancer rates have risen steadily in recent years, and it is now the leading cause of cancer death for people younger than 50 in the United States, according to the American Cancer Society.
An expert in biomechanics and mechanobiology, Ferruzzi said that this work was motivated by clinical observations by Huang.
“Our team brought an engineering mindset to the table to understand the physical mechanisms involved in early-onset colorectal cancer,” Ferruzzi said.
Ferruzzi’s lab is located in the Texas Instruments Biomedical Engineering and Sciences Building on the UTSW East Campus. The building, which houses labs for UT Dallas and UTSW researchers, is designed to foster collaboration between the institutions.
The colon is a flexible cylindrical tube that uses coordinated muscle contractions to push waste out of the human body. The tube can stiffen, however, when the extracellular material, a load-bearing mesh made of collagen within the colon wall, thickens or becomes abnormally remodeled due to inflammation or fibrosis.
UT Dallas researchers performed biomechanical testing on tissue samples obtained from colorectal-cancer patients undergoing surgical resection at UTSW. For the study, the team collected tissue from 19 patients above the age of 50 who had been diagnosed with average-onset colorectal cancer, and from 14 patients below the age of 50 who were diagnosed with early-onset colorectal cancer.
Researchers performed microindention tests, which involve pressing a tiny probe into the tissue to measure its resistance to pressure, and measured how the samples responded to compression. The results of these tests were supported by structural and genetic analyses. In combination, their work demonstrated that the cancerous and noncancerous tissue in the early-onset patients was fibrotic, or scarlike, and contained more collagen, a protein that normally holds tissues together but also makes them abnormally stiff when collagen is too abundant.
“We know from previous studies that cancers are usually stiffer than normal tissues,” Ferruzzi said. “While this was true also in patients with early-onset colorectal cancer, we were surprised to find that both healthy and cancerous tissues from these younger patients were stiffer than those from older patients. This led our team to think that such stiffness could be creating a favorable environment for cancer to develop early in life.”
To understand how this may happen, researchers cultured cancer cells on biomaterials that reproduce the physical properties of biological tissues. They found that cancer cells in stiff environments were more likely to proliferate, demonstrating that mechanical stiffness enables cancer cells to grow more aggressively.
In addition to studying tissue samples and cancer cells in a dish, the researchers grew patient-derived organoids — miniaturized 3D microtissues that mimic the complexity of the organ of origin. The organoid experiments confirmed that a stiff environment can push cancer cells to grow at a faster rate regardless of whether the original donor was young or old.
Ferruzzi said he hopes the research will lead to better treatments and prevention of early-onset colorectal cancer.
UT Dallas and UT Southwestern Medical Center researchers worked together on the early-onset colorectal cancer study at the Texas Instruments Biomedical Engineering and Sciences Building.
“If we can understand how physical forces fuel colorectal-cancer progression, then we can actually think about early diagnosis and, possibly, therapy,” Ferruzzi said. “More importantly, we can ask the question: How do we stop people from developing cancer that early in life?”
UT Dallas authors include first co-authors Nicole C. Huning BS’24 and Victor V. Nguyen, a doctoral student in the UT Dallas joint biomedical engineering program in collaboration with UTSW; Haider A. Ali BS’24; Adil Khan, a doctoral student in Ferruzzi’s Tissue Mechanics & Remodeling Laboratory; and Dr. Victor Varner , associate professor of bioengineering.
Other study authors include collaborators from UTSW and Washington University in St. Louis.
The project was partially funded by the UT Dallas Office of Research and Innovation through a $125,000 Collaborative Biomedical Research Award , a seed grant to encourage interdisciplinary collaborations. As an undergraduate, Huning received a UT Dallas Bioengineering Researchers award to support the project.
Additional support came from the National Institutes of Health ( R01CA237304-05 , U01CA214300 , P30CA142543 ), the Burroughs Wellcome Fund, the American Society of Colon & Rectal Surgeons, and the UTSW Whole Brain Microscopy Facility.
Advanced Science
Experimental study
Human tissue samples
Biomechanical Phenotyping Reveals Unique Mechanobiological Signatures of Early-Onset Colorectal Cancer
1-Dec-2025
The authors declare no conflict of interest.