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Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models

Roughly one third of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-sensitive mutated (EGFRm) tumors experience disease progression through central nervous system (CNS) metastases during treatment. Although EGFR-TKIs have been r...

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Autores principales: Zhang, Yuhan, Zhang, Yaoshuai, Niu, Wenwen, Ge, Xianming, Huang, Fuhao, Pang, Jinlong, Li, Xian, Wang, Yu, Gao, Wei, Fan, Fangtian, Li, Shanshan, Liu, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497791/
https://www.ncbi.nlm.nih.gov/pubmed/34630120
http://dx.doi.org/10.3389/fphar.2021.750031
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author Zhang, Yuhan
Zhang, Yaoshuai
Niu, Wenwen
Ge, Xianming
Huang, Fuhao
Pang, Jinlong
Li, Xian
Wang, Yu
Gao, Wei
Fan, Fangtian
Li, Shanshan
Liu, Hao
author_facet Zhang, Yuhan
Zhang, Yaoshuai
Niu, Wenwen
Ge, Xianming
Huang, Fuhao
Pang, Jinlong
Li, Xian
Wang, Yu
Gao, Wei
Fan, Fangtian
Li, Shanshan
Liu, Hao
author_sort Zhang, Yuhan
collection PubMed
description Roughly one third of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-sensitive mutated (EGFRm) tumors experience disease progression through central nervous system (CNS) metastases during treatment. Although EGFR-TKIs have been reported to be favored in some patients with EGFRm NSCLC CNS metastases, novel EGFR-TKIs with proven efficacy in CNS pathologies are clinically needed.To investigate whether almonertinib, a novel third-generation EGFR-TKI for NSCLC, can cross the blood-brain barrier (BBB) and deliver treatment for EGFR-mutant NSCLC brain metastases and spinal cord metastases, we constructed NSCLC brain metastasis and spinal cord metastasis models in vivo to observe the anti-tumor effects of almonertinib. Using ABCB1-MDCK and BCRP-MDCK monolayer cells as the in vitro study model, the effects of transport time and drug concentration on the apparent permeability coefficient of almonertinib and its active metabolite, HAS-719, were investigated. The results of this study show that almonertinib can significantly inhibit PC9 brain and spinal cord metastases. Pharmacokinetic studies in mice revealed that almonertinib has good BBB penetration ability, whereas the metabolite HAS-719 does not easily penetrate the BBB. Early clinical evidence of almonertinib activity in patients with EGFRm-advanced NSCLC and brain metastases has also been reported. In conclusion, almonertinib easily penetrates the BBB and inhibits advanced NSCLC brain and spinal cord metastases.
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spelling pubmed-84977912021-10-09 Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models Zhang, Yuhan Zhang, Yaoshuai Niu, Wenwen Ge, Xianming Huang, Fuhao Pang, Jinlong Li, Xian Wang, Yu Gao, Wei Fan, Fangtian Li, Shanshan Liu, Hao Front Pharmacol Pharmacology Roughly one third of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-sensitive mutated (EGFRm) tumors experience disease progression through central nervous system (CNS) metastases during treatment. Although EGFR-TKIs have been reported to be favored in some patients with EGFRm NSCLC CNS metastases, novel EGFR-TKIs with proven efficacy in CNS pathologies are clinically needed.To investigate whether almonertinib, a novel third-generation EGFR-TKI for NSCLC, can cross the blood-brain barrier (BBB) and deliver treatment for EGFR-mutant NSCLC brain metastases and spinal cord metastases, we constructed NSCLC brain metastasis and spinal cord metastasis models in vivo to observe the anti-tumor effects of almonertinib. Using ABCB1-MDCK and BCRP-MDCK monolayer cells as the in vitro study model, the effects of transport time and drug concentration on the apparent permeability coefficient of almonertinib and its active metabolite, HAS-719, were investigated. The results of this study show that almonertinib can significantly inhibit PC9 brain and spinal cord metastases. Pharmacokinetic studies in mice revealed that almonertinib has good BBB penetration ability, whereas the metabolite HAS-719 does not easily penetrate the BBB. Early clinical evidence of almonertinib activity in patients with EGFRm-advanced NSCLC and brain metastases has also been reported. In conclusion, almonertinib easily penetrates the BBB and inhibits advanced NSCLC brain and spinal cord metastases. Frontiers Media S.A. 2021-09-24 /pmc/articles/PMC8497791/ /pubmed/34630120 http://dx.doi.org/10.3389/fphar.2021.750031 Text en Copyright © 2021 Zhang, Zhang, Niu, Ge, Huang, Pang, Li, Wang, Gao, Fan, Li and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Yuhan
Zhang, Yaoshuai
Niu, Wenwen
Ge, Xianming
Huang, Fuhao
Pang, Jinlong
Li, Xian
Wang, Yu
Gao, Wei
Fan, Fangtian
Li, Shanshan
Liu, Hao
Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models
title Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models
title_full Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models
title_fullStr Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models
title_full_unstemmed Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models
title_short Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models
title_sort experimental study of almonertinib crossing the blood-brain barrier in egfr-mutant nsclc brain metastasis and spinal cord metastasis models
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497791/
https://www.ncbi.nlm.nih.gov/pubmed/34630120
http://dx.doi.org/10.3389/fphar.2021.750031
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