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The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview

Pancreatic ductal adenocarcinoma (PDAC) has one of the highest mortality rates among all cancer types. Its delayed diagnosis precludes curative resection, thus most of the current therapies against PDAC are based on chemo- and radiotherapy. Unfortunately, these strategies are insufficient to improve...

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Autores principales: Quiñonero, Francisco, Mesas, Cristina, Doello, Kevin, Cabeza, Laura, Perazzoli, Gloria, Jimenez-Luna, Cristina, Rama, Ana Rosa, Melguizo, Consolación, Prados, Jose
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chinese Anti-Cancer Association 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936232/
https://www.ncbi.nlm.nih.gov/pubmed/31908888
http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0252
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author Quiñonero, Francisco
Mesas, Cristina
Doello, Kevin
Cabeza, Laura
Perazzoli, Gloria
Jimenez-Luna, Cristina
Rama, Ana Rosa
Melguizo, Consolación
Prados, Jose
author_facet Quiñonero, Francisco
Mesas, Cristina
Doello, Kevin
Cabeza, Laura
Perazzoli, Gloria
Jimenez-Luna, Cristina
Rama, Ana Rosa
Melguizo, Consolación
Prados, Jose
author_sort Quiñonero, Francisco
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) has one of the highest mortality rates among all cancer types. Its delayed diagnosis precludes curative resection, thus most of the current therapies against PDAC are based on chemo- and radiotherapy. Unfortunately, these strategies are insufficient to improve its poor prognosis. Despite the advances made in chemotherapy (e.g. nab-paclitaxel and gemcitabine), many patients with PDAC are unable to benefit from them due to the rapid development of drug resistance. Currently, more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors, including different integrins, mucins, NF-κB, RAS and CXCR4. Moreover, drug resistance in PDAC is thought to be mediated by the modulation of miRNAs (e.g. miRNA-21, miRNA-145 and miRNA-155), which regulate genes that participate in cell proliferation, invasion and metastasis. Finally, cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes -involved in drug transport-, and enzymes such as aldehyde dehydrogenases -implicated in cellular drug metabolism- and poly (ADP-ribose) polymerases -involved in drug-induced DNA damage repair. Understanding the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC.
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spelling pubmed-69362322020-01-06 The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview Quiñonero, Francisco Mesas, Cristina Doello, Kevin Cabeza, Laura Perazzoli, Gloria Jimenez-Luna, Cristina Rama, Ana Rosa Melguizo, Consolación Prados, Jose Cancer Biol Med Review Pancreatic ductal adenocarcinoma (PDAC) has one of the highest mortality rates among all cancer types. Its delayed diagnosis precludes curative resection, thus most of the current therapies against PDAC are based on chemo- and radiotherapy. Unfortunately, these strategies are insufficient to improve its poor prognosis. Despite the advances made in chemotherapy (e.g. nab-paclitaxel and gemcitabine), many patients with PDAC are unable to benefit from them due to the rapid development of drug resistance. Currently, more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors, including different integrins, mucins, NF-κB, RAS and CXCR4. Moreover, drug resistance in PDAC is thought to be mediated by the modulation of miRNAs (e.g. miRNA-21, miRNA-145 and miRNA-155), which regulate genes that participate in cell proliferation, invasion and metastasis. Finally, cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes -involved in drug transport-, and enzymes such as aldehyde dehydrogenases -implicated in cellular drug metabolism- and poly (ADP-ribose) polymerases -involved in drug-induced DNA damage repair. Understanding the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC. Chinese Anti-Cancer Association 2019-11 /pmc/articles/PMC6936232/ /pubmed/31908888 http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0252 Text en Copyright 2019 Cancer Biology & Medicine http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Review
Quiñonero, Francisco
Mesas, Cristina
Doello, Kevin
Cabeza, Laura
Perazzoli, Gloria
Jimenez-Luna, Cristina
Rama, Ana Rosa
Melguizo, Consolación
Prados, Jose
The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview
title The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview
title_full The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview
title_fullStr The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview
title_full_unstemmed The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview
title_short The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview
title_sort challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936232/
https://www.ncbi.nlm.nih.gov/pubmed/31908888
http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0252
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