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Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier
The incidence of brain metastases has been increasing constantly for the last 20 years, because of better control of metastases outside the brain, and the failure of most drugs to cross the blood–brain barrier at relevant pharmacological concentrations. Recent advances in the molecular biology of ca...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468523/ https://www.ncbi.nlm.nih.gov/pubmed/34575525 http://dx.doi.org/10.3390/pharmaceutics13091446 |
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author | Angeli, Eurydice Bousquet, Guilhem |
author_facet | Angeli, Eurydice Bousquet, Guilhem |
author_sort | Angeli, Eurydice |
collection | PubMed |
description | The incidence of brain metastases has been increasing constantly for the last 20 years, because of better control of metastases outside the brain, and the failure of most drugs to cross the blood–brain barrier at relevant pharmacological concentrations. Recent advances in the molecular biology of cancer have led to the identification of numerous molecular alterations, some of them targetable with the development of specific targeted therapies, including tyrosine kinase inhibitors. In this narrative review, we set out to describe the state-of-the-art in the use of tyrosine kinase inhibitors for the treatment of melanoma, lung cancer, and breast cancer brain metastases. We also report preclinical and clinical pharmacological data on brain exposure to tyrosine kinase inhibitors after oral administration and describe the most recent advances liable to facilitate their penetration of the blood–brain barrier at relevant concentrations and limit their physiological efflux. |
format | Online Article Text |
id | pubmed-8468523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84685232021-09-27 Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier Angeli, Eurydice Bousquet, Guilhem Pharmaceutics Review The incidence of brain metastases has been increasing constantly for the last 20 years, because of better control of metastases outside the brain, and the failure of most drugs to cross the blood–brain barrier at relevant pharmacological concentrations. Recent advances in the molecular biology of cancer have led to the identification of numerous molecular alterations, some of them targetable with the development of specific targeted therapies, including tyrosine kinase inhibitors. In this narrative review, we set out to describe the state-of-the-art in the use of tyrosine kinase inhibitors for the treatment of melanoma, lung cancer, and breast cancer brain metastases. We also report preclinical and clinical pharmacological data on brain exposure to tyrosine kinase inhibitors after oral administration and describe the most recent advances liable to facilitate their penetration of the blood–brain barrier at relevant concentrations and limit their physiological efflux. MDPI 2021-09-10 /pmc/articles/PMC8468523/ /pubmed/34575525 http://dx.doi.org/10.3390/pharmaceutics13091446 Text en © 2021 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 Angeli, Eurydice Bousquet, Guilhem Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier |
title | Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier |
title_full | Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier |
title_fullStr | Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier |
title_full_unstemmed | Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier |
title_short | Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier |
title_sort | brain metastasis treatment: the place of tyrosine kinase inhibitors and how to facilitate their diffusion across the blood–brain barrier |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468523/ https://www.ncbi.nlm.nih.gov/pubmed/34575525 http://dx.doi.org/10.3390/pharmaceutics13091446 |
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