ArticleBritish journal of cancer2015
OATP1B1 and tumour OATP1B3 modulate exposure, toxicity, and survival after irinotecan-based chemotherapy.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 75 citations in OpenAlex.
- A Comprehensive Review on Irinotecan-Induced Delayed Diarrhea: From Mechanisms to Therapeutic Options.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Development of an adult whole-body PBPK model of irinotecan and its metabolites for predicting UGT1A1/CYP3A-mediated drug-drug interactions.Frontiers in pharmacology · 2026Article
- Article
- Regulation of the Organic Anion Transporting Polypeptide 1B3 (OATP1B3) by Sex Hormones.Bulletin of experimental biology and medicine · 2024Article
- Irinotecan-Induced Toxicity: A Pharmacogenetic Study Beyond UGT1A1.Clinical pharmacokinetics · 2023Article
- Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease.Frontiers in pharmacology · 2023Article
- Review
- Evaluation of pharmacogenomics and hepatic nuclear imaging-related covariates by population pharmacokinetic models of irinotecan and its metabolites.European journal of clinical pharmacology · 2022Article
- Associations betweenFrontiers in pediatrics · 2022Article
- Minimal contribution of the hepatic uptake transporter OATP1B1 to the inter-individual variability in SN-38 pharmacokinetics in cancer patients without severe renal failure.Cancer chemotherapy and pharmacology · 2021Article
- Quantitative Investigation of Irinotecan Metabolism, Transport, and Gut Microbiome Activation.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- Multi-factorial pharmacokinetic interactions: unraveling complexities in precision drug therapy.Expert opinion on drug metabolism & toxicology · 2021Review
- Hepatobiliary phase enhancement of liver metastases on gadoxetic acid MRI: assessment of frequency and patterns.European radiology · 2021Article
- Hepatobiliary contrast uptake patterns on gadoxetic acid-enhanced MRI in liver metastases from pancreatic ductal adenocarcinoma: can it predict prognosis?European radiology · 2021Article
- The Road so Far in Colorectal Cancer Pharmacogenomics: Are We Closer to Individualised Treatment?Journal of personalized medicine · 2020Review
- Two common polymorphic variants of OATP4A1 as potential risk factors for colorectal cancer.Oncology letters · 2020Article
- Cellular Mechanisms Accounting for the Refractoriness of Colorectal Carcinoma to Pharmacological Treatment.Cancers · 2020Review
- Review
- Characterization of organic anion transporting polypeptide 1b2 knockout rats generated by CRISPR/Cas9: a novel model for drug transport and hyperbilirubinemia disease.Acta pharmaceutica Sinica. B · 2020Article
- Pharmacogenomics, biomarker network, and allele frequencies in colorectal cancer.The pharmacogenomics journal · 2020Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTreatment of advanced and metastatic colorectal cancer with irinotecan is hampered by severe toxicities. The active metabolite of irinotecan, SN-38, is a known substrate of drug-metabolising enzymes, including UGT1A1, as well as OATP and ABC drug transporters.
methodsBlood samples (n=127) and tumour tissue (n=30) were obtained from advanced cancer patients treated with irinotecan-based regimens for pharmacogenetic and drug level analysis and transporter expression. Clinical variables, toxicity, and outcomes data were collected.
resultsSLCO1B1 521C was significantly associated with increased SN-38 exposure (P<0.001), which was additive with UGT1A1*28. ABCC5 (rs562) carriers had significantly reduced SN-38 glucuronide and APC metabolite levels. Reduced risk of neutropenia and diarrhoea was associated with ABCC2-24C/T (odds ratio (OR)=0.22, 0.06-0.85) and CES1 (rs2244613; OR=0.29, 0.09-0.89), respectively. Progression-free survival (PFS) was significantly longer in SLCO1B1 388G/G patients and reduced in ABCC2-24T/T and UGT1A1*28 carriers. Notably, higher OATP1B3 tumour expression was associated with reduced PFS.
conclusionsClarifying the association of host genetic variation in OATP and ABC transporters to SN-38 exposure, toxicity and PFS provides rationale for personalising irinotecan-based chemotherapy. Our findings suggest that OATP polymorphisms and expression in tumour tissue may serve as important new biomarkers.
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