Novel High-Throughput Drug Screening Platform for Chemotherapy-Induced Axonal Neuropathy
Final rept. 1 May 2011-30 Apr 2014
JOHNS HOPKINS UNIV BALTIMORE MD
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Chemotherapy-induced peripheral neuropathy CIPN is the most common dose-limiting neurotoxicity from anti-cancer drug therapy 1,2. Platinum drugs, taxanes, proteasome inhibitors, vinca alkaloids, epothilones, and immunomodulators are the standard of anti-cancer therapies for the six most cancers. An estimated 2010 incidence of 994, 680 cases for these six cancers is reported. Therapeutic clinical trials indicate from 25 to 100 of CIPN with symptoms lasting months to years. Several hundred thousand patients per year are experiencing CIPN. The number of cancer survivors living with CIPN is unknown. Even when CIPN does not involve dose-limiting side effects, its onset may severely affect the patient s quality of life and can cause dosage reductions, delay in treatment, and even treatment discontinuation 3. The pathologic changes in most cases of CIPN revolve around the distal to proximal axonal degeneration, rather than cell body death, which has been referred to as dying-back neuropathy. 4 Currently, there are no effective therapies aimed at halting the progression of, or reversing distal axonal degeneration through, the usage of anti-breast cancer drugs 5. All of the available therapies are aimed at symptomatic control of neuropathic pain however they do not protect against the underlying issue of distal axonal degeneration.
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