期刊
NEUROPHARMACOLOGY
卷 76, 期 -, 页码 175-183出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2013.08.016
关键词
Paclitaxel; Taxol; Chemotherapy; Peripheral neuropathy; Microtubule dynamics; Neurotoxicity
资金
- NIGMS NIH HHS [R01 GM069808] Funding Source: Medline
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM069808] Funding Source: NIH RePORTER
Paclitaxel is a microtubule-binding compound that is widely used as a chemotherapeutic in the treatment of common cancers, including breast and ovarian cancer. Paclitaxel binding along the length of microtubules stabilizes them and suppresses their dynamics, leading to mitotic arrest and apoptosis in dividing cells. Though they are not dividing cells, neurons are also susceptible to paclitaxel, and paclitaxel exposure results in axonal degeneration. Thus a frequent side effect of paclitaxel treatment in patients is peripheral neuropathy, which can necessitate dose reductions and have lasting symptoms. An understanding of the mechanisms underlying paclitaxel's neurotoxicity is important for development of therapeutics to prevent and alleviate the neuropathy. Here we will review approaches taken to investigate mechanisms of paclitaxel-induced neuropathy and evidence for potential mechanisms of the axonal degeneration downstream of or distinct from microtubule stabilization by paclitaxel. (C) 2013 Elsevier Ltd. All rights reserved.
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