ArticleClinical pharmacology and therapeutics2022
Quantitative Proteomics of Hepatic Drug-Metabolizing Enzymes and Transporters in Patients With Colorectal Cancer Metastasis.
Article in Clinical pharmacology and therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Pooled it
- Overlooked aspects of scaling enzyme activity through abundance across tissues and individuals: Insights from kDrug metabolism and disposition: the biological fate of chemicals · 2026Article
- A liquid biopsy-RNAseq method for monitoring the expression of genes involved in drug disposition: Proof-of-concept application to cholestatic liver disease.Journal of pharmaceutical and biomedical analysis · 2026Article
- Personalized Medicine Approach to Proteomics and Metabolomics of Cytochrome P450 Enzymes: A Narrative Review.European journal of drug metabolism and pharmacokinetics · 2024Review
- A guide to developing population files for physiologically-based pharmacokinetic modeling in the Simcyp Simulator.CPT: pharmacometrics & systems pharmacology · 2024Article
- Identification of Rab7 as an autophagy marker: potential therapeutic approaches and the effect of Qi Teng Xiao Zhuo granule in chronic glomerulonephritis.Pharmaceutical biology · 2023Article
- The Role ofInternational journal of molecular sciences · 2023Article
- The Role of Solute Carrier Transporters in Efficient Anticancer Drug Delivery and Therapy.Pharmaceutics · 2023Review
- Proteomic quantification of receptor tyrosine kinases involved in the development and progression of colorectal cancer liver metastasis.Frontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The impact of liver cancer metastasis on protein abundance of 22 drug-metabolizing enzymes (DMEs) and 25 transporters was investigated using liquid chromatography-tandem accurate mass spectrometry targeted proteomics. Microsomes were prepared from liver tissue taken from 15 healthy individuals and 18 patients with cancer (2 primary and 16 metastatic). Patient samples included tumors and matching histologically normal tissue. The levels of cytochrome P450 (CYPs 2B6, 2D6, 2E1, 3A4, and 3A5) and uridine 5'-diphospho-glucuronosyltransferases (UGTs 1A1, 1A6, 1A9, 2B15, 2B4, and 2B7) were lower in histologically normal tissue from patients relative to healthy controls (up to 6.6-fold) and decreased further in tumors (up to 21-fold for CYPs and 58-fold for UGTs). BSEP and MRPs were also suppressed in histologically normal (up to 3.1-fold) and tumorous tissue (up to 6.3-fold) relative to healthy individuals. Abundance of OCT3, OAT2, OAT7, and OATPs followed similar trends (up to 2.9-fold lower in histologically normal tissue and up to 16-fold lower in tumors). Abundance of NTCP and OCT1 was also lower (up to 9-fold). Interestingly, monocarboxylate transporter MCT1 was more abundant (3.3-fold) in tumors, the only protein target to show this pattern. These perturbations could be attributed to inflammation. Interindividual variability was substantially higher in patients with cancer. Proteomics-informed physiologically-based pharmacokinetic (PBPK) models of 50 drugs with different attributes and hepatic extraction ratios (Simcyp) showed substantially lower drug clearance with cancer-specific parameters compared with default parameters. In conclusion, this study provides values for decreased abundance of DMEs and transporters in liver cancer, which enables using population-specific abundance for these patients in PBPK modeling.
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