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Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy

Cancer cells utilise several mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocy...

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Autores principales: Kryczka, Jolanta, Kryczka, Jakub, Czarnecka-Chrebelska, Karolina H., Brzeziańska-Lasota, Ewa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396273/
https://www.ncbi.nlm.nih.gov/pubmed/34445588
http://dx.doi.org/10.3390/ijms22168885
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author Kryczka, Jolanta
Kryczka, Jakub
Czarnecka-Chrebelska, Karolina H.
Brzeziańska-Lasota, Ewa
author_facet Kryczka, Jolanta
Kryczka, Jakub
Czarnecka-Chrebelska, Karolina H.
Brzeziańska-Lasota, Ewa
author_sort Kryczka, Jolanta
collection PubMed
description Cancer cells utilise several mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm, and epigenetic regulation by microRNAs (miRNAs). Because it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced, and the cancer cells may have acquired drug resistance. This review summarises the main mechanisms involved in cisplatin resistance and interactions between cisplatin-resistant cancer cells and the tumour microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin-resistant non-small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly dysregulated TP53, MDM2, and CDKN1A genes as they encode the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.
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spelling pubmed-83962732021-08-28 Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy Kryczka, Jolanta Kryczka, Jakub Czarnecka-Chrebelska, Karolina H. Brzeziańska-Lasota, Ewa Int J Mol Sci Review Cancer cells utilise several mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm, and epigenetic regulation by microRNAs (miRNAs). Because it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced, and the cancer cells may have acquired drug resistance. This review summarises the main mechanisms involved in cisplatin resistance and interactions between cisplatin-resistant cancer cells and the tumour microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin-resistant non-small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly dysregulated TP53, MDM2, and CDKN1A genes as they encode the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis. MDPI 2021-08-18 /pmc/articles/PMC8396273/ /pubmed/34445588 http://dx.doi.org/10.3390/ijms22168885 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
Kryczka, Jolanta
Kryczka, Jakub
Czarnecka-Chrebelska, Karolina H.
Brzeziańska-Lasota, Ewa
Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy
title Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy
title_full Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy
title_fullStr Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy
title_full_unstemmed Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy
title_short Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy
title_sort molecular mechanisms of chemoresistance induced by cisplatin in nsclc cancer therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396273/
https://www.ncbi.nlm.nih.gov/pubmed/34445588
http://dx.doi.org/10.3390/ijms22168885
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