ArticleCancers2021
PXR Modulates the Prostate Cancer Cell Response to Afatinib by Regulating the Expression of the Monocarboxylate Transporter SLC16A1.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Recent progress in small molecules targeting the acidic tumor microenvironment.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- The role of MCT1 in tumor progression and targeted therapy: a comprehensive review.Frontiers in immunology · 2025Review
- Unsymmetrical Bisacridines' Interactions with ABC Transporters and Their Cellular Impact on Colon LS 174T and Prostate DU 145 Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Research on molecular characteristics of ADME-related genes in kidney renal clear cell carcinoma.Scientific reports · 2024Article
- Identification of Molecular Markers Associated with Prostate Cancer Subtypes: An Integrative Bioinformatics Approach.Biomolecules · 2024Article
- Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Metabolic Profiling and Investigation of the Modulatory Effect ofAntioxidants (Basel, Switzerland) · 2023Article
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- The System Profile of Renal Drug Transporters in Tubulointerstitial Fibrosis Model and Consequent Effect on Pharmacokinetics.Molecules (Basel, Switzerland) · 2022Article
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Authors and funding
16 authors.
Funding
Abstract
Resistance to castration is a crucial issue in the treatment of metastatic prostate cancer. Kinase inhibitors (KIs) have been tested as potential alternatives, but none of them are approved yet. KIs are subject of extensive metabolism at both the hepatic and the tumor level. Here, we studied the role of PXR (Pregnane X Receptor), a master regulator of metabolism, in the resistance to KIs in a prostate cancer setting. We confirmed that PXR is expressed in prostate tumors and is more frequently detected in advanced forms of the disease. We showed that stable expression of PXR in 22Rv1 prostate cancer cells conferred a resistance to dasatinib and a higher sensitivity to erlotinib, dabrafenib, and afatinib. Higher sensitivity to afatinib was due to a ~ 2-fold increase in its intracellular accumulation and involved the SLC16A1 transporter as its pharmacological inhibition by BAY-8002 suppressed sensitization of 22Rv1 cells to afatinib and was accompanied with reduced intracellular concentration of the drug. We found that PXR could bind to the
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Registered trials
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