Platinum neurotoxicity pharmacogenetics.
Cisplatin, carboplatin, and oxaliplatin anticancer drugs are commonly used to treat lung, colorectal, ovarian, breast, head and neck, and genitourinary cancers. However, the efficacy of platinum-based drugs is often compromised because of the substantial risk for severe toxicities, including neurotoxicity. Neurotoxicity can result in both acute and chronic debilitation. Moreover, colorectal cancer patients treated with oxaliplatin discontinue therapy more often because of peripheral neuropathy than tumor progression, potentially compromising patient benefit. Numerous methods to prevent neurotoxicity have thus far proven unsuccessful. To circumvent this life-altering side effect while taking advantage of the antitumor activities of the platinum agents, efforts to identify mechanism-based biomarkers are under way. In this review, we detail findings from the current literature for genetic markers associated with neurotoxicity induced by single-agent and combination platinum chemotherapy. These data have the potential for broad clinical implications if mechanistic associations lead to the development of toxicity modulators to minimize the noxious sequelae of platinum chemotherapy.
McWhinney
Sarah R
SR
School of Pharmacy, Institute for Pharmacogenomics and Individualized Therapy, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Campus Box 7360, 3203 Kerr Hall, Chapel Hill, NC 27599-7360, USA.
Goldberg
Richard M
RM
McLeod
Howard L
HL
D000818:Animals; D004260:DNA Repair / Q000187:drug effects; D004351:Drug Resistance / Q000187:drug effects; D016678:Genome / Q000235:genetics; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000235:genetics*; D010597:Pharmacogenetics; D017671:Platinum Compounds / Q000009:adverse effects* / Q000737:chemistry / Q000633:toxicity
D017671:Platinum Compounds