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Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma
Gastric adenocarcinoma (GAC) is the most common histological type of gastric cancer, the fifth according to the frequency and the third among the deadliest cancers. GAC high mortality is due to a combination of factors, such as silent evolution, late clinical presentation, underlying genetic heterog...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463778/ https://www.ncbi.nlm.nih.gov/pubmed/32751679 http://dx.doi.org/10.3390/cancers12082116 |
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author | Marin, Jose J. G. Perez-Silva, Laura Macias, Rocio I. R. Asensio, Maitane Peleteiro-Vigil, Ana Sanchez-Martin, Anabel Cives-Losada, Candela Sanchon-Sanchez, Paula Sanchez De Blas, Beatriz Herraez, Elisa Briz, Oscar Lozano, Elisa |
author_facet | Marin, Jose J. G. Perez-Silva, Laura Macias, Rocio I. R. Asensio, Maitane Peleteiro-Vigil, Ana Sanchez-Martin, Anabel Cives-Losada, Candela Sanchon-Sanchez, Paula Sanchez De Blas, Beatriz Herraez, Elisa Briz, Oscar Lozano, Elisa |
author_sort | Marin, Jose J. G. |
collection | PubMed |
description | Gastric adenocarcinoma (GAC) is the most common histological type of gastric cancer, the fifth according to the frequency and the third among the deadliest cancers. GAC high mortality is due to a combination of factors, such as silent evolution, late clinical presentation, underlying genetic heterogeneity, and effective mechanisms of chemoresistance (MOCs) that make the available antitumor drugs scarcely useful. MOCs include reduced drug uptake (MOC-1a), enhanced drug efflux (MOC-1b), low proportion of active agents in tumor cells due to impaired pro-drug activation or active drug inactivation (MOC-2), changes in molecular targets sensitive to anticancer drugs (MOC-3), enhanced ability of cancer cells to repair drug-induced DNA damage (MOC-4), decreased function of pro-apoptotic factors versus up-regulation of anti-apoptotic genes (MOC-5), changes in tumor cell microenvironment altering the response to anticancer agents (MOC-6), and phenotypic transformations, including epithelial-mesenchymal transition (EMT) and the appearance of stemness characteristics (MOC-7). This review summarizes updated information regarding the molecular bases accounting for these mechanisms and their impact on the lack of clinical response to the pharmacological treatment currently used in GAC. This knowledge is required to identify novel biomarkers to predict treatment failure and druggable targets, and to develop sensitizing strategies to overcome drug refractoriness in GAC. |
format | Online Article Text |
id | pubmed-7463778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74637782020-09-02 Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma Marin, Jose J. G. Perez-Silva, Laura Macias, Rocio I. R. Asensio, Maitane Peleteiro-Vigil, Ana Sanchez-Martin, Anabel Cives-Losada, Candela Sanchon-Sanchez, Paula Sanchez De Blas, Beatriz Herraez, Elisa Briz, Oscar Lozano, Elisa Cancers (Basel) Review Gastric adenocarcinoma (GAC) is the most common histological type of gastric cancer, the fifth according to the frequency and the third among the deadliest cancers. GAC high mortality is due to a combination of factors, such as silent evolution, late clinical presentation, underlying genetic heterogeneity, and effective mechanisms of chemoresistance (MOCs) that make the available antitumor drugs scarcely useful. MOCs include reduced drug uptake (MOC-1a), enhanced drug efflux (MOC-1b), low proportion of active agents in tumor cells due to impaired pro-drug activation or active drug inactivation (MOC-2), changes in molecular targets sensitive to anticancer drugs (MOC-3), enhanced ability of cancer cells to repair drug-induced DNA damage (MOC-4), decreased function of pro-apoptotic factors versus up-regulation of anti-apoptotic genes (MOC-5), changes in tumor cell microenvironment altering the response to anticancer agents (MOC-6), and phenotypic transformations, including epithelial-mesenchymal transition (EMT) and the appearance of stemness characteristics (MOC-7). This review summarizes updated information regarding the molecular bases accounting for these mechanisms and their impact on the lack of clinical response to the pharmacological treatment currently used in GAC. This knowledge is required to identify novel biomarkers to predict treatment failure and druggable targets, and to develop sensitizing strategies to overcome drug refractoriness in GAC. MDPI 2020-07-30 /pmc/articles/PMC7463778/ /pubmed/32751679 http://dx.doi.org/10.3390/cancers12082116 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Marin, Jose J. G. Perez-Silva, Laura Macias, Rocio I. R. Asensio, Maitane Peleteiro-Vigil, Ana Sanchez-Martin, Anabel Cives-Losada, Candela Sanchon-Sanchez, Paula Sanchez De Blas, Beatriz Herraez, Elisa Briz, Oscar Lozano, Elisa Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma |
title | Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma |
title_full | Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma |
title_fullStr | Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma |
title_full_unstemmed | Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma |
title_short | Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma |
title_sort | molecular bases of mechanisms accounting for drug resistance in gastric adenocarcinoma |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463778/ https://www.ncbi.nlm.nih.gov/pubmed/32751679 http://dx.doi.org/10.3390/cancers12082116 |
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