Overview

• Earliest-stage tumors in engineered mice expanded in white matter, damaged axons, and triggered SARM1-mediated clearance that coincided with a shift to more aggressive behavior.
• Genetic loss of SARM1 kept damaged axons intact, delayed tumor aggressiveness, extended survival, and preserved neurological function nearly to end of life.
• Experimentally increasing axonal injury accelerated tumor progression, reinforcing a causal role for the injury-clearance pathway.
• SARM1 inhibitors under early development for neurodegenerative conditions are candidates for repurposing, with additional preclinical testing required before any patient trials.
• Blocking axon degeneration did not stop growth entirely, suggesting future strategies would likely pair axon protection with surgery, radiotherapy, or chemotherapy in a cancer with 12–18 month average survival.