Colorectal cancer may result in tumor-related inflammation that damages peripheral nerves before even starting cancer treatment, according to preclinical findings published in Nature Communications. This damage may be the reason why colorectal cancer survivors are more likely to develop peripheral neuropathy.
“These findings advance our understanding of how colorectal cancer can cause damage to the peripheral nervous system,” said senior study author Andrew Shepherd, PhD, Associate Professor of Translational Neuroscience at The University of Texas MD Anderson Cancer Center. “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.”
Background and Study Methods
Survivors of colorectal cancer are at an increased risk for developing neurological issues, such as peripheral neuropathy. Researchers looked at mouse and primate models of colorectal cancer to determine the cause of these neurological issues.
Key Findings
The researchers showed that mice with colorectal cancer also developed peripheral neuropathy, which was associated with subtle locomotor deficits, without overt hypersensitivity.
Widespread differences were found in pro-inflammatory cytokines and lipid metabolites in the peripheral nerves of the tumor-bearing mice. Macrophage accumulation, myelin decompaction, and ryanodine receptor oxidation were all associated with dysfunctional calcium homeostasis as well as less spike amplitude in sensory neurons.
Alterations in both plasma inflammatory mediators and lipid metabolites were associated with neuropathy and macrophage accumulation in the peripheral nerves of the primate models with colorectal cancer.
“These findings suggest colorectal cancer is causally linked to a subacute form of chronic inflammatory demyelinating polyneuropathy across species, which may represent an underreported yet important risk factor for neurological dysfunction in colorectal cancer survivors,” the study authors concluded.
Additional research is also needed to determine if the findings are consistent in humans and explore nerve function before, during, and after chemotherapy.
DISCLOSURES: This study was funded by the U.S. Department of Defense, the UT MD Anderson Cancer Neuroscience Program, a Rita Allen Foundation Award, the Cancer Prevention and Research Institute of Texas (CPRIT), and the National Institutes of Health. For full disclosures of the study authors, visit nature.com.
