Grant: Project Grant

Nerve damage is a common adverse side-effect of cancer chemotherapy. Chemotherapy-induced neuropathy (CTIN) can cause severe pain and reduce ability to walk, write, button a shirt, or pick up coins. CTIN can last for weeks, months, or even years after treatment is done. Severe CTIN can cause more serious problems, including dangerous falls, changes in heart rate and blood pressure and trouble breathing. Despite the widespread incidence of CTIN, the specific mechanisms that cause it are not well understood and there are currently no treatments available to prevent or recover from CTIN. During development, more neurons are made than can be used and for the nervous system to function properly, excess neurons must be destroyed. The initial step in this process is the loss of neuronal axons which are destroyed through an active signaling process. The overarching hypothesis in this proposal is that chemotherapeutic agents destroy axons by activating the signaling processes that exist to destroy sensory axons during normal development. Our goals are identify the signaling processes that drive DRG axon destruction, and determine which of these are activated in CTIN.