Why DNA Repair Accidentally Causes Chemotherapy-Induced Neurotoxicity

Did you know that your brain's own repair crew can accidentally destroy your nerves? It sounds wild, but it is exactly what happens during cancer treatment. Standard cancer drugs like cisplatin kill tumours but also cause chemotherapy-induced neurotoxicity. This nerve damage leaves patients with severe, burning pain in their hands and feet. For years, scientists did not know why. Researchers found that neurons use a mechanism called Nucleotide Excision Repair (NER) to fix DNA damage. In normal cells, NER is a lifesaver. But neurons do not divide and only keep a tiny stash of dNTPs—the basic building blocks of DNA.

The Mechanism Behind Chemotherapy-Induced Neurotoxicity

When NER starts fixing the chemo damage, it quickly drains this tiny dNTP stash. Because the neuron runs out of parts, the repair fails. This leaves the DNA with massive double-strand breaks, triggering cell death. The cool part? Researchers found that supplementing neurons with deoxynucleosides refuels their dNTP stash. In lab models, this simple boost:

• Restores the cell's nucleotide pools
• Prevents DNA double-strand breaks
• Reduces painful nerve damage

This suggests that simple nutrient supplements could one day help patients undergo chemo without suffering from chronic nerve pain.