Nerve damage, or neuropathy, is a common side effect of chemotherapy
This preclinical study found that colorectal tumors were associated with subtle nerve inflammation and damage even prior to chemotherapy treatment
The damage developed without pain sensitivity, which may explain why it has gone unrecognized
Findings suggest that some nerves are more vulnerable to treatment-related injury
HOUSTON, AUGUST 2026 ― Researchers at The University of Texas MD Anderson Cancer Center found that, in preclinical models of colorectal cancer, tumors can start damaging peripheral nerves before chemotherapy begins. These findings suggest tumor-related inflammation and changes to fat metabolism could damage the protective coating around nerves, disrupting signals and potentially making them more vulnerable to treatment-induced peripheral neuropathy, or nerve damage.
The study, published in Nature Communications1 and led by Andrew Shepherd, Ph.D., associate professor of Translational Neuroscience, challenges the conventional thought that peripheral neuropathy in patients with colorectal cancer is due mostly to chemotherapy treatment. Rather, the findings suggest that much of the nerve damage may already be present because of the cancer itself, even without overt pain symptoms.
“These findings advance our understanding of how colorectal cancer can cause damage to the peripheral nervous system,” Shepherd said.
“This nerve damage, which affects the protective insulation around nerves, is largely latent and could have major implications for quality of life in survivors, even when there are no obvious pain symptoms.”Andrew Shepherd, Ph.D., Associate Professor of Translational Neuroscience
In preclinical models of colorectal cancer, researchers observed a loss of small nerve fibers in the skin and subtle problems with movement and coordination. However, there was no clear sensitivity to touch or temperature, suggesting that neuropathy could occur without obvious pain symptoms.
Further analyses revealed damage to myelin sheaths, the protective material surrounding nerve fibers, as well as signs of stress in the cells that produce and maintain myelin. Additionally, the nerve cells showed problems regulating calcium, which helps transmit signals. These changes were accompanied by weaker electrical signals and reduced nerve-cell activity.
The researchers also found changes in inflammatory proteins and fat molecules associated with inflammation in the blood and nerves. Macrophages – immune cells that respond to injuries – also accumulated in peripheral sensory nerves. However, removing these cells exacerbated movement problems in the models, meaning that some macrophages may actually play a protective or reparative role.
Treatment with an anti-inflammatory drug reduced some early abnormalities but did not prevent all signs of nerve injury, implying that inflammation contributes to neuropathy but is not the only factor involved.
Together, the results suggest a model in which tumor-driven inflammation and altered fat metabolism contribute to stress and damage in peripheral nerves. The findings also raise questions about whether subtle nerve damage before treatment makes patients more vulnerable to later neurological side effects.
While these findings were consistent in preclinical models that developed colorectal cancer naturally and, in turn, suggest that this phenomenon occurs across species, the study did not include human samples or patient outcomes. Additional research is also needed to examine nerve function in patients before, during and after chemotherapy to determine whether neuropathy occurs similarly across different colorectal cancer subtypes.
Reference:
1) https://www.nature.com/articles/s41467-026-76683-1
(Newswise/HG)