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The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are i...

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Autores principales: Zhou, Jiabei, Kang, Yu, Chen, Lu, Wang, Hua, Liu, Junqing, Zeng, Su, Yu, Lushan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100275/
https://www.ncbi.nlm.nih.gov/pubmed/32265714
http://dx.doi.org/10.3389/fphar.2020.00343
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author Zhou, Jiabei
Kang, Yu
Chen, Lu
Wang, Hua
Liu, Junqing
Zeng, Su
Yu, Lushan
author_facet Zhou, Jiabei
Kang, Yu
Chen, Lu
Wang, Hua
Liu, Junqing
Zeng, Su
Yu, Lushan
author_sort Zhou, Jiabei
collection PubMed
description Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum–DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.
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spelling pubmed-71002752020-04-07 The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents Zhou, Jiabei Kang, Yu Chen, Lu Wang, Hua Liu, Junqing Zeng, Su Yu, Lushan Front Pharmacol Pharmacology Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum–DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely. Frontiers Media S.A. 2020-03-20 /pmc/articles/PMC7100275/ /pubmed/32265714 http://dx.doi.org/10.3389/fphar.2020.00343 Text en Copyright © 2020 Zhou, Kang, Chen, Wang, Liu, Zeng and Yu http://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
Zhou, Jiabei
Kang, Yu
Chen, Lu
Wang, Hua
Liu, Junqing
Zeng, Su
Yu, Lushan
The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents
title The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents
title_full The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents
title_fullStr The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents
title_full_unstemmed The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents
title_short The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents
title_sort drug-resistance mechanisms of five platinum-based antitumor agents
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100275/
https://www.ncbi.nlm.nih.gov/pubmed/32265714
http://dx.doi.org/10.3389/fphar.2020.00343
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