Neurodegeneration rewires the tumor microenvironment via the neuro-immune-cancer axis.

Neurodegeneration and cancer, long considered opposing processes, neuronal loss versus uncontrolled proliferation, are increasingly recognized as mechanistically convergent. We propose a mechanistic, target-based therapeutic classification that transcends disease boundaries.

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• 1 This review reframes the field by positioning neurodegeneration as an active driver of tumor evolution.
• 2 Integrating insights from multi-omics, spatial transcriptomics, and neuroimmune-microbiota studies, we show how degenerating neurons disrupt DNA repair, mitochondrial function, immune regulation, and barrier integrity, thereby creating tumor-permissive niches.
• 3 Particular emphasis is placed on the enteric nervous system, where neuronal loss promotes colorectal and pancreatic cancers through immune suppression and microbial dysbiosis.

Understanding this could lead to better treatments, improved diagnostics, or a deeper grasp of how the human body works — benefiting patient care globally.

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