Aside from dose capping, there are currently no effective treatments for vincristine-induced peripheral neuropathy.
Vincristine is one of the most important chemotherapy drugs used to treat a range of paediatric cancers including acute lymphoblastic leukaemia, sarcoma, medulloblastoma and neuroblastoma. However, one of its major side effects is vincristine-induced neuropathy, which not only significantly reduces the quality of life of patients but can also necessitate dose reduction or discontinuation of treatment.
Vincristine-induced peripheral sensory neuropathy (VIPN) is characterised by numbness, tingling and neuropathic pain in the extremities, disabling loss of sensory discrimination, and distal motor weakness that arises from damage to peripheral nerves.
The Vetter lab has recently obtained new evidence demonstrating that development of VIPN is based on activation of specific inflammatory pathways by vincristine, and that treatment with a drug used to treat rheumatoid arthritis entirely prevents this debilitating side effect of chemotherapy.
The aim of this proposal is to define the molecular mechanisms of VIPN and to characterise the analgesic effects of anti-inflammatory treatments. As these treatments are based on the repurposing of existing drugs, Associate Professor Vetter’s research will permit the rapid translation of these findings to clinical trials, and improvements of the quality of life of children treated with vincristine.