CONTROLLING ROS IN PLATINUM-INDUCED PERIPHERAL NEUROPATHY: THERAPEUTIC APPLICATIONS

Platinum-based chemotherapies, while being efficient at preventing tumor growth, display several types of toxicities many of which present as neurological impairments. Oxaliplatin indicated in cancers of the colon, stomach and ovaries induces two forms of peripheral neuropathies, namely acute and chronic. While the acute form translates as transitory cold hyperalgesia which resolves within hours to days following first infusion, the chronic form resulting from cumulative high doses translates as irreversible paresthesia and cold hypoesthesia which represent a limiting-factor for its use in therapeutics. Oxaliplatin anti-tumor efficacy has been linked to ROS-induced apoptosis of tumor cells through GSH depletion. ROS being ubiquitously toxic, neuronal cells exposed degenerate upon administration of oxaliplatin. Relying on differential basal cell-specific GSH production while modulating pro-inflammatory pathways activated by these ROS may be beneficial in addressing neurodegenerative processes in patients suffering from oxaliplatin-induced peripheral neuropathies.