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The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of Tyrosine Kinase Inhibitors

Tyrosine kinase inhibitors (TKIs) decisively contributed in revolutionizing the therapeutic approach to cancer, offering non-invasive, tolerable therapies for a better quality of life. Nonetheless, degree and duration of the response to TKI therapy vary depending on cancer molecular features, the ab...

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Autores principales: Xiu, Fangrui, Rausch, Magdalena, Gai, Zhibo, Su, Shanshan, Wang, Shijun, Visentin, Michele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917293/
https://www.ncbi.nlm.nih.gov/pubmed/36768423
http://dx.doi.org/10.3390/ijms24032101
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author Xiu, Fangrui
Rausch, Magdalena
Gai, Zhibo
Su, Shanshan
Wang, Shijun
Visentin, Michele
author_facet Xiu, Fangrui
Rausch, Magdalena
Gai, Zhibo
Su, Shanshan
Wang, Shijun
Visentin, Michele
author_sort Xiu, Fangrui
collection PubMed
description Tyrosine kinase inhibitors (TKIs) decisively contributed in revolutionizing the therapeutic approach to cancer, offering non-invasive, tolerable therapies for a better quality of life. Nonetheless, degree and duration of the response to TKI therapy vary depending on cancer molecular features, the ability of developing resistance to the drug, on pharmacokinetic alterations caused by germline variants and unwanted drug–drug interactions at the level of membrane transporters and metabolizing enzymes. A great deal of approved TKIs are inhibitors of the organic cation transporters (OCTs). A handful are also substrates of them. These transporters are polyspecific and highly expressed in normal epithelia, particularly the intestine, liver and kidney, and are, hence, arguably relevant sites of TKI interactions with other OCT substrates. Moreover, OCTs are often repressed in cancer cells and might contribute to the resistance of cancer cells to TKIs. This article reviews the OCT interactions with approved and in-development TKIs reported in vitro and in vivo and critically discusses the potential clinical ramifications thereof.
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spelling pubmed-99172932023-02-11 The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of Tyrosine Kinase Inhibitors Xiu, Fangrui Rausch, Magdalena Gai, Zhibo Su, Shanshan Wang, Shijun Visentin, Michele Int J Mol Sci Review Tyrosine kinase inhibitors (TKIs) decisively contributed in revolutionizing the therapeutic approach to cancer, offering non-invasive, tolerable therapies for a better quality of life. Nonetheless, degree and duration of the response to TKI therapy vary depending on cancer molecular features, the ability of developing resistance to the drug, on pharmacokinetic alterations caused by germline variants and unwanted drug–drug interactions at the level of membrane transporters and metabolizing enzymes. A great deal of approved TKIs are inhibitors of the organic cation transporters (OCTs). A handful are also substrates of them. These transporters are polyspecific and highly expressed in normal epithelia, particularly the intestine, liver and kidney, and are, hence, arguably relevant sites of TKI interactions with other OCT substrates. Moreover, OCTs are often repressed in cancer cells and might contribute to the resistance of cancer cells to TKIs. This article reviews the OCT interactions with approved and in-development TKIs reported in vitro and in vivo and critically discusses the potential clinical ramifications thereof. MDPI 2023-01-20 /pmc/articles/PMC9917293/ /pubmed/36768423 http://dx.doi.org/10.3390/ijms24032101 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Xiu, Fangrui
Rausch, Magdalena
Gai, Zhibo
Su, Shanshan
Wang, Shijun
Visentin, Michele
The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of Tyrosine Kinase Inhibitors
title The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of Tyrosine Kinase Inhibitors
title_full The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of Tyrosine Kinase Inhibitors
title_fullStr The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of Tyrosine Kinase Inhibitors
title_full_unstemmed The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of Tyrosine Kinase Inhibitors
title_short The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of Tyrosine Kinase Inhibitors
title_sort role of organic cation transporters in the pharmacokinetics, pharmacodynamics and drug–drug interactions of tyrosine kinase inhibitors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917293/
https://www.ncbi.nlm.nih.gov/pubmed/36768423
http://dx.doi.org/10.3390/ijms24032101
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