RGD Reference Report - Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity. - Rat Genome Database

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Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity.

Authors: Filipski, KK  Mathijssen, RH  Mikkelsen, TS  Schinkel, AH  Sparreboom, A 
Citation: Filipski KK, etal., Clin Pharmacol Ther. 2009 Oct;86(4):396-402. doi: 10.1038/clpt.2009.139. Epub 2009 Jul 22.
RGD ID: 7243884
Pubmed: PMID:19625999   (View Abstract at PubMed)
PMCID: PMC2746866   (View Article at PubMed Central)
DOI: DOI:10.1038/clpt.2009.139   (Journal Full-text)

Cisplatin is one of the most widely used anticancer agents for the treatment of solid tumors. The clinical use of cisplatin is associated with dose-limiting nephrotoxicity, which occurs in one-third of patients despite intensive prophylactic measures. Organic cation transporter 2 (OCT2) has been implicated in the cellular uptake of cisplatin, but its role in cisplatin-induced nephrotoxicity remains unknown. In mice, deletion of Oct1 and Oct2 resulted in significantly impaired urinary excretion of cisplatin without an apparent influence on plasma levels. Furthermore, the Oct1/Oct2-deficient mice were protected from severe cisplatin-induced renal tubular damage. Subsequently, we found that a nonsynonymous single-nucleotide polymorphism (SNP) in the OCT2 gene SLC22A2 (rs316019) was associated with reduced cisplatin-induced nephrotoxicity in patients. Collectively, these results indicate the critical importance of OCT2 in the renal handling and related renal toxicity of cisplatin and provide a rationale for the development of new targeted approaches to mitigate this debilitating side effect.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SLC22A2Humanacute kidney failure susceptibilityIAGP DNA:SNP: :808G>T (rs316019) humanRGD 
Slc22a2Ratacute kidney failure susceptibilityISOSLC22A2 (Homo sapiens)DNA:SNP: :808G>T (rs316019) humanRGD 
Slc22a2Mouseacute kidney failure susceptibilityISOSLC22A2 (Homo sapiens)DNA:SNP: :808G>T (rs316019) humanRGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc22a2  (solute carrier family 22 member 2)

Genes (Mus musculus)
Slc22a2  (solute carrier family 22 (organic cation transporter), member 2)

Genes (Homo sapiens)
SLC22A2  (solute carrier family 22 member 2)


Additional Information