title: Central neurotoxicity in cancer chemotherapy: pharmacogenetic insights.
abstract: Central neurotoxicity of chemotherapy is likely to be multifactorial. There are two hypotheses regarding endogenous mechanisms that may be involved, namely the target and the blood-brain barrier transporter hypotheses. Here, we will review candidate genetic determinants for the risk of chemotherapy-induced neurotoxicity, such as polymorphisms involved in the target mechanism. These include polymorphisms in folate metabolizing enzymes and apolipoprotein E, as well as those in blood-brain barrier transporter genes. Currently, the exact role of pharmacogenetics in mechanisms that lead to central neurotoxicity of chemotherapy has not been fully unraveled. Larger, prospective, longitudinal and more uniform studies are needed, with prechemotherapy and follow-up measurements of neuropsychological performance, MRI, PET, genetic profiles and biomarkers relevant for the proposed target and transporter mechanisms.
authors: VU University Medical Center, Department of Neurology, Amsterdam, The Netherlands. f.froklage@vumc.nl
authors: Femke E A M
authors: FE
authors: Froklage
authors: Jaap C
authors: JC
authors: Reijneveld
authors: Jan J
authors: JJ
authors: Heimans
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000235:genetics; D001812:Blood-Brain Barrier; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D020258:Neurotoxicity Syndromes / Q000235:genetics*; D010597:Pharmacogenetics / Q000639:trends; D011110:Polymorphism, Genetic
chemical_list: D000970:Antineoplastic Agents; D001057:Apolipoproteins E; D008727:Methotrexate