Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1784886335339757568 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9917293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT xiufangrui theroleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors AT rauschmagdalena theroleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors AT gaizhibo theroleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors AT sushanshan theroleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors AT wangshijun theroleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors AT visentinmichele theroleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors AT xiufangrui roleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors AT rauschmagdalena roleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors AT gaizhibo roleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors AT sushanshan roleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors AT wangshijun roleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors AT visentinmichele roleoforganiccationtransportersinthepharmacokineticspharmacodynamicsanddrugdruginteractionsoftyrosinekinaseinhibitors |