Colorectal tumors may damage peripheral nerves before chemotherapy begins
核心洞察
Researchers at UT MD Anderson found that, in preclinical models of colorectal cancer (搜索), tumors can damage peripheral nerves before any chemotherapy is given.
The nerve damage affects the protective myelin insulation and is largely latent, occurring without obvious pain symptoms, yet may affect survivors' quality of life.
Tumor-driven inflammation and altered fat metabolism appear to contribute to nerve stress and damage, though inflammation is not the only factor involved.
Researchers at The University of Texas MD Anderson Cancer Center have found that, in preclinical models of colorectal cancer (搜索), tumors can begin damaging peripheral nerves before chemotherapy is even initiated. The study, published in Nature Communications and led by Andrew Shepherd, Ph.D., associate professor of Translational Neuroscience, challenges the conventional view that peripheral neuropathy (搜索) in colorectal cancer patients is due mostly to chemotherapy treatment. Instead, 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 (搜索) 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."
Understanding peripheral neuropathy and why it is difficult to recognize
Peripheral neuropathy (搜索) occurs when nerves outside of the brain and spinal cord become damaged. This damage can cause pain, numbness, balance problems, weakness and/or reduced sensitivity to touch and temperature. Chemotherapy is commonly used to treat colorectal cancers, and some drugs can cause peripheral neuropathy and associated symptoms. The researchers sought to understand and identify possible cancer-related nerve changes prior to treatment in order to reduce the risk of patients developing chronic pain.
Previous research has shown reduced nerve-fiber density and sensory dysfunction in preclinical models prior to receiving chemotherapy, but these changes are usually considered mild and may not be recognized as signs of nerve damage. Properly identifying this damage could help researchers understand why some patients develop more severe or persistent symptoms after treatment. Studies such as this are part of UT MD Anderson's Cancer Neuroscience Program, a first-of-its-kind initiative that examines the interactions between cancer and the nervous system, taking a multidisciplinary approach to enhance patient quality of life.
Signs of nerve injury in preclinical models
In preclinical models of colorectal cancer (搜索), 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.
Implications for patients with colorectal cancer
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 (搜索) naturally — suggesting that this phenomenon occurs across species — the study did not include human samples or patient outcomes. Additional research is needed to examine nerve function in patients before, during and after chemotherapy to determine whether neuropathy occurs similarly across different colorectal cancer subtypes.