ArticleMolecular cancer therapeutics2015
Severely Impaired and Dysregulated Cytochrome P450 Expression and Activities in Hepatocellular Carcinoma: Implications for Personalized Treatment in Patients.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 68 citations in OpenAlex.
- Article
- Spatial transcriptomic-metabolic features of tumor foci and tumor capsule in microvascular invasion with hepatocellular carcinoma: A spatial multi-omics study.PLoS medicine · 2026Article
- Article
- Integrated bioinformatics and molecular docking ıdentify CCNB1, CDK1, and CYP1A2 as therapeutic targets of phytochemicals in hepatocellular carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- CYP2A6 suppresses hepatocellular carcinoma via inhibiting SRC/Wnt/β-Catenin pathway.Acta pharmacologica Sinica · 2025Article
- Roles of organic anion transporting polypeptides in hepatocellular carcinoma.Frontiers in genetics · 2025Article
- Gut microbiota trigger host liver immune responses that affect drug-metabolising enzymes.Frontiers in immunology · 2024Review
- High-expressed PTPN1 promotes tumor proliferation signature in human hepatocellular carcinoma.Heliyon · 2023Article
- Vascularized Hepatocellular Carcinoma on a Chip to Control Chemoresistance through Cirrhosis, Inflammation and Metabolic Activity.Small structures · 2023Article
- Quantitative Proteomics of Hepatic Drug-Metabolizing Enzymes and Transporters in Patients With Colorectal Cancer Metastasis.Clinical pharmacology and therapeutics · 2022Article
- Genomic and transcriptomic somatic alterations of hepatocellular carcinoma in non-cirrhotic livers.Cancer genetics · 2022Article
- Proteomics of colorectal cancer liver metastasis: A quantitative focus on drug elimination and pharmacodynamics effects.British journal of clinical pharmacology · 2022Article
- Role of miR-653 and miR-29c in downregulation of CYP1A2 expression in hepatocellular carcinoma.Pharmacological reports : PR · 2022Article
- Bioinformatics screening the novel and promising targets of curcumin in hepatocellular carcinoma chemotherapy and prognosis.BMC complementary medicine and therapies · 2022Article
- Article
- Development and Validation of a Metabolic-related Prognostic Model for Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2021Article
- How to Treat Hepatocellular Carcinoma in Elderly Patients.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Involvement of cytochrome P450 enzymes in inflammation and cancer: a review.Cancer chemotherapy and pharmacology · 2021Review
- Tumor Microenvironment Alters Chemoresistance of Hepatocellular Carcinoma Through CYP3A4 Metabolic Activity.Frontiers in oncology · 2021Article
- Population Pharmacokinetics of CC-122.Clinical pharmacology : advances and applications · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
This study aims to systematically determine the activities and expressions of cytochrome P450s (CYP) in hepatocellular carcinoma (HCC) patients to support their optimal use in personalized treatment of HCC. Activities of seven major drug-metabolizing CYP enzymes (CYP1A2, 2A6, 2C8, 2C9, 2D6, 2E1, and 3A4) were determined in tumors and pericarcinomatous tissues harvested from 26 patients with hepatitis B virus-positive HCC using probe substrates. Protein and mRNA levels of these CYPs were also measured using isotope label-free LC/MS-MS method and real-time PCR, respectively. Maximal metabolic velocity (Vmax) of CYP probe substrates was decreased by 2.5- to 30-fold in tumor microsomes, accompanied by a corresponding decrease in their protein and mRNA expression levels. However, Km values and turnover numbers of substrates in tumor microsomes were not changed. High correlations between activities and CYP protein levels were also observed, but the correlation between activities and mRNA levels was often poor. There was a major decrease in the degree of correlation in CYP expression in tumor tissues, suggesting that CYP expression levels are greatly disrupted by the tumorigenic process. Our unprecedented systemic study of the effects of HCC on CYPs demonstrated that activities of CYPs were seriously impaired and their expression patterns were severely altered by HCC. We proposed that determination of the CYP protein expression profile by LC/MS-MS in each patient is a promising approach that can be clinically used for individualized treatment of HCC.
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