Irinotecan pathway (Rattus norvegicus)
From WikiPathways
Description
This pathway shows the biotransformation of the chemotherapy prodrug irinotecan to form the active metabolite SN-38, an inhibitor of DNA topoisomerase I. SN-38 is primarily metabolized to the inactive SN-38 glucuronide by UGT1A1, the isoform catalyzing bilirubin glucuronidation. Irinotecan is used in the treatment of metastatic colorectal cancer, small cell lung cancer and several other solid tumors. There is large interpatient variability in response to irinotecan, as well as severe side effects such as diarrhea and neutropenia, which might be explained in part by genetic variation in the metabolic enzymes and transporters depicted here. Well-known variants to effect this pathway are the promoter polymorphic repeat in UGT1A1 (UGT1A1*28) and the 1236C>T polymorphism in ABCB1. While UGT1A1*28 genotype has been associated with toxicity, further evidence is needed to describe the roles of ABCB1 variants in toxicity.
Source: PharmGkb
Quality Tags
Ontology Terms
Bibliography
- Desai AA, Innocenti F, Ratain MJ; ''UGT pharmacogenomics: implications for cancer risk and cancer therapeutics.''; Pharmacogenetics, 2003 PubMed Europe PMC Scholia
- Mathijssen RH, Marsh S, Karlsson MO, Xie R, Baker SD, Verweij J, Sparreboom A, McLeod HL; ''Irinotecan pathway genotype analysis to predict pharmacokinetics.''; Clin Cancer Res, 2003 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
APC | Metabolite | CHEBI:80551 (ChEBI) | |
Abcc1 | GeneProduct | 24565 (Entrez Gene) | |
Abcc2 | GeneProduct | 25303 (Entrez Gene) | |
Abcg2 | GeneProduct | 312382 (Entrez Gene) | |
Bche | GeneProduct | 65036 (Entrez Gene) | |
CYP3A4 | GeneProduct | 1576 (Entrez Gene) | |
CYP3A5 | GeneProduct | 1577 (Entrez Gene) | |
Ces2 | GeneProduct | 171118 (Entrez Gene) | |
Irinotecan | Metabolite | 54825 (Chemspider) | |
Irinotecan | Metabolite | CHEBI:80630 (ChEBI) | |
M4 | Metabolite | molecular weight, 558 | |
NPC1 | GeneProduct | 4864 (Entrez Gene) | |
RGD:621508 | GeneProduct | 29225 (Entrez Gene) | |
SN-38 | Metabolite | CHEBI:8988 (ChEBI) | |
SN-38G | Metabolite | CHEBI:8990 (ChEBI) | |
UGT1A10 | GeneProduct | 54575 (Entrez Gene) | |
UGT1A9 | GeneProduct | 396552 (Entrez Gene) | |
Ugt1a1 | GeneProduct | 24861 (Entrez Gene) | |
Ugt1a6 | GeneProduct | 113992 (Entrez Gene) |
Annotated Interactions
No annotated interactions