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...
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| Veröffentlicht in: | Cancers 2020-08, Vol.12 (8), p.2116 |
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| creator | 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 |
| 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. |
| doi_str_mv | 10.3390/cancers12082116 |
| format | Article |
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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</creator><creatorcontrib>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</creatorcontrib><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.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers12082116</identifier><identifier>PMID: 32751679</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Adenocarcinoma ; Antitumor agents ; Apoptosis ; Biopsy ; Cancer therapies ; Chemoresistance ; Chemotherapy ; DNA damage ; DNA repair ; Drug resistance ; Drug therapy ; Gastric cancer ; Gene regulation ; Genotype & phenotype ; Mesenchyme ; Observations ; Physiological aspects ; Proteins ; Review ; Tumor cells ; Tumors</subject><ispartof>Cancers, 2020-08, Vol.12 (8), p.2116</ispartof><rights>COPYRIGHT 2020 MDPI AG</rights><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c426t-6cc8bfcc792443c9b57ec0c5bea7bb09ec266ab79560ebe8ff38da27113d11d3</citedby><cites>FETCH-LOGICAL-c426t-6cc8bfcc792443c9b57ec0c5bea7bb09ec266ab79560ebe8ff38da27113d11d3</cites><orcidid>0000-0001-6891-1554 ; 0000-0002-4748-0326 ; 0000-0001-9271-3320 ; 0000-0003-1186-6849 ; 0000-0003-2649-8778</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463778/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463778/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27907,27908,53774,53776</link.rule.ids></links><search><creatorcontrib>Marin, Jose J. G.</creatorcontrib><creatorcontrib>Perez-Silva, Laura</creatorcontrib><creatorcontrib>Macias, Rocio I. R.</creatorcontrib><creatorcontrib>Asensio, Maitane</creatorcontrib><creatorcontrib>Peleteiro-Vigil, Ana</creatorcontrib><creatorcontrib>Sanchez-Martin, Anabel</creatorcontrib><creatorcontrib>Cives-Losada, Candela</creatorcontrib><creatorcontrib>Sanchon-Sanchez, Paula</creatorcontrib><creatorcontrib>Sanchez De Blas, Beatriz</creatorcontrib><creatorcontrib>Herraez, Elisa</creatorcontrib><creatorcontrib>Briz, Oscar</creatorcontrib><creatorcontrib>Lozano, Elisa</creatorcontrib><title>Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma</title><title>Cancers</title><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.</description><subject>Adenocarcinoma</subject><subject>Antitumor agents</subject><subject>Apoptosis</subject><subject>Biopsy</subject><subject>Cancer therapies</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>DNA damage</subject><subject>DNA repair</subject><subject>Drug resistance</subject><subject>Drug therapy</subject><subject>Gastric cancer</subject><subject>Gene regulation</subject><subject>Genotype & phenotype</subject><subject>Mesenchyme</subject><subject>Observations</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Review</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc9LHTEQx4O0qFjPXgNevLyaH7uTzUV4ta0tKIUiXkN2dvYZ2U002S3437uvirbOZQbmw_c7w5exIyk-a23FKfqIlItUolFSwg7bV8KoFYCtPvwz77HDUu7EUlpLA2aX7WllagnG7rObqzQQzoPP_IsvVHjq-RXhrY-hjIWvEdMcpxA3vE-Zf83zhv-mEsq09eYh8gtfphyQrzuKCX3GENPoP7GPvR8KHb70A3b9_dv1-Y_V5a-Ln-fryxVWCqYVIDZtj2isqiqNtq0NocC6JW_aVlhCBeBbY2sQ1FLT97rpvDJS6k7KTh-ws2fZ-7kdqUOKU_aDu89h9PnRJR_c_5sYbt0m_XGmAm1MswicvAjk9DBTmdwYCtIw-EhpLk5VWoARUNsFPX6H3qU5x-W7v5RSWgK8URs_kAuxT4svbkXdGrS1YLWtFur0mcKcSsnUv54shdtm695lq58Ar4uXVg</recordid><startdate>20200801</startdate><enddate>20200801</enddate><creator>Marin, Jose J. 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G.</au><au>Perez-Silva, Laura</au><au>Macias, Rocio I. R.</au><au>Asensio, Maitane</au><au>Peleteiro-Vigil, Ana</au><au>Sanchez-Martin, Anabel</au><au>Cives-Losada, Candela</au><au>Sanchon-Sanchez, Paula</au><au>Sanchez De Blas, Beatriz</au><au>Herraez, Elisa</au><au>Briz, Oscar</au><au>Lozano, Elisa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma</atitle><jtitle>Cancers</jtitle><date>2020-08-01</date><risdate>2020</risdate><volume>12</volume><issue>8</issue><spage>2116</spage><pages>2116-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>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.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>32751679</pmid><doi>10.3390/cancers12082116</doi><orcidid>https://orcid.org/0000-0001-6891-1554</orcidid><orcidid>https://orcid.org/0000-0002-4748-0326</orcidid><orcidid>https://orcid.org/0000-0001-9271-3320</orcidid><orcidid>https://orcid.org/0000-0003-1186-6849</orcidid><orcidid>https://orcid.org/0000-0003-2649-8778</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma Antitumor agents Apoptosis Biopsy Cancer therapies Chemoresistance Chemotherapy DNA damage DNA repair Drug resistance Drug therapy Gastric cancer Gene regulation Genotype & phenotype Mesenchyme Observations Physiological aspects Proteins Review Tumor cells Tumors |
| title | Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma |
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