ArticleDrug metabolism and disposition: the biological fate of chemicals2012
Sulfation of 4-hydroxy toremifene: individual variability, isoform specificity, and contribution to toremifene pharmacogenomics.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Treating ER-positive breast cancer: a review of the current FDA-approved SERMs and SERDs and their mechanisms of action.Oncology reviews · 2025Review
- Estrogen Sulfotransferase (SULT1E1): Its Molecular Regulation, Polymorphisms, and Clinical Perspectives.Journal of personalized medicine · 2021Review
- Influence ofPharmacogenomics and personalized medicine · 2021Article
- A high frequency missense SULT1B1 allelic variant (L145V) selectively expressed in African descendants exhibits altered kinetic properties.Xenobiotica; the fate of foreign compounds in biological systems · 2018Article
- Rare genetic variants in cellular transporters, metabolic enzymes, and nuclear receptors can be important determinants of interindividual differences in drug response.Genetics in medicine : official journal of the American College of Medical Genetics · 2017Article
- Effect of MRP2 and MRP3 Polymorphisms on Anastrozole Glucuronidation and MRP2 and MRP3 Gene Expression in Normal Liver Samples.International journal of cancer research and molecular mechanisms · 2015Article
- Pharmacogenetics of SULT1A1.Pharmacogenomics · 2014Article
- A potential role for human UDP-glucuronosyltransferase 1A4 promoter single nucleotide polymorphisms in the pharmacogenomics of tamoxifen and its derivatives.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Sulfotransferase 1A1 (SULT1A1) gene expression is regulated by members of the NFI transcription factors in human breast cancer cells.BMC clinical pathology · 2014Article
- Sulfotransferase genetic variation: from cancer risk to treatment response.Drug metabolism reviews · 2013Review
- Potential role of UGT1A4 promoter SNPs in anastrozole pharmacogenomics.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Copy number variation in sulfotransferase isoform 1A1 (SULT1A1) is significantly associated with enzymatic activity in Japanese subjects.Pharmacogenomics and personalized medicine · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Toremifene (TOR) is a selective estrogen receptor modulator used in adjuvant therapy for breast cancer and in clinical trials for prostate cancer prevention. The chemical structure of TOR differs from that of tamoxifen (TAM) by the presence of a chlorine atom in the ethyl side chain, resulting in a more favorable toxicity spectrum with TOR. In addition, some patients who fail on TAM therapy benefit from high-dose TOR therapy. Several studies have indicated that functional genetic variants in the TAM metabolic pathway influence response to therapy, but pharmacogenomic studies of patients treated with TOR are lacking. In this study, we examined individual variability in sulfation of 4-hydroxy TOR (4-OH TOR) (the active metabolite of TOR) in human liver cytosols from 104 subjects and found approximately 30-fold variation in activity. 4-OH TOR sulfation was significantly correlated (r = 0.98, P < 0.0001) with β-naphthol sulfation (diagnostic for SULT1A1) but not with 17β estradiol sulfation, a diagnostic substrate for SULT1E1(r = 0.09, P = 0.34). Examination of recombinant sulfotransferases (SULTs) revealed that SULT1A1 and SULT1E1 catalyzed 4-OH TOR sulfation, with apparent Km values of 2.6 and 6.4 μM and Vmax values of 8.5 and 5.5 nmol x min(-1) x mg protein(-1), respectively. 4-OH TOR sulfation was inhibited by 2,6-dichloro-4-nitrophenol (IC50 = 2.34 ± 0.19 μM), a specific inhibitor of SULT1A1. There was also a significant association between SULT1A1 genotypes and copy number and 4-OH TOR sulfation in human liver cytosols. These results indicate that variability in sulfation could contribute to response to TOR in the treatment of breast and prostate cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.