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Stress-activated kinases as therapeutic targets in pancreatic cancer

Pancreatic cancer is a dismal disease with high incidence and poor survival rates. With the aim to improve overall survival of pancreatic cancer patients, new therapeutic approaches are urgently needed. Protein kinases are key regulatory players in basically all stages of development, maintaining ph...

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Autores principales: Traub, Benno, Roth, Aileen, Kornmann, Marko, Knippschild, Uwe, Bischof, Joachim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384741/
https://www.ncbi.nlm.nih.gov/pubmed/34497429
http://dx.doi.org/10.3748/wjg.v27.i30.4963
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author Traub, Benno
Roth, Aileen
Kornmann, Marko
Knippschild, Uwe
Bischof, Joachim
author_facet Traub, Benno
Roth, Aileen
Kornmann, Marko
Knippschild, Uwe
Bischof, Joachim
author_sort Traub, Benno
collection PubMed
description Pancreatic cancer is a dismal disease with high incidence and poor survival rates. With the aim to improve overall survival of pancreatic cancer patients, new therapeutic approaches are urgently needed. Protein kinases are key regulatory players in basically all stages of development, maintaining physiologic functions but also being involved in pathogenic processes. c-Jun N-terminal kinases (JNK) and p38 kinases, representatives of the mitogen-activated protein kinases, as well as the casein kinase 1 (CK1) family of protein kinases are important mediators of adequate response to cellular stress following inflammatory and metabolic stressors, DNA damage, and others. In their physiologic roles, they are responsible for the regulation of cell cycle progression, cell proliferation and differentiation, and apoptosis. Dysregulation of the underlying pathways consequently has been identified in various cancer types, including pancreatic cancer. Pharmacological targeting of those pathways has been the field of interest for several years. While success in earlier studies was limited due to lacking specificity and off-target effects, more recent improvements in small molecule inhibitor design against stress-activated protein kinases and their use in combination therapies have shown promising in vitro results. Consequently, targeting of JNK, p38, and CK1 protein kinase family members may actually be of particular interest in the field of precision medicine in patients with highly deregulated kinase pathways related to these kinases. However, further studies are warranted, especially involving in vivo investigation and clinical trials, in order to advance inhibition of stress-activated kinases to the field of translational medicine.
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spelling pubmed-83847412021-09-07 Stress-activated kinases as therapeutic targets in pancreatic cancer Traub, Benno Roth, Aileen Kornmann, Marko Knippschild, Uwe Bischof, Joachim World J Gastroenterol Review Pancreatic cancer is a dismal disease with high incidence and poor survival rates. With the aim to improve overall survival of pancreatic cancer patients, new therapeutic approaches are urgently needed. Protein kinases are key regulatory players in basically all stages of development, maintaining physiologic functions but also being involved in pathogenic processes. c-Jun N-terminal kinases (JNK) and p38 kinases, representatives of the mitogen-activated protein kinases, as well as the casein kinase 1 (CK1) family of protein kinases are important mediators of adequate response to cellular stress following inflammatory and metabolic stressors, DNA damage, and others. In their physiologic roles, they are responsible for the regulation of cell cycle progression, cell proliferation and differentiation, and apoptosis. Dysregulation of the underlying pathways consequently has been identified in various cancer types, including pancreatic cancer. Pharmacological targeting of those pathways has been the field of interest for several years. While success in earlier studies was limited due to lacking specificity and off-target effects, more recent improvements in small molecule inhibitor design against stress-activated protein kinases and their use in combination therapies have shown promising in vitro results. Consequently, targeting of JNK, p38, and CK1 protein kinase family members may actually be of particular interest in the field of precision medicine in patients with highly deregulated kinase pathways related to these kinases. However, further studies are warranted, especially involving in vivo investigation and clinical trials, in order to advance inhibition of stress-activated kinases to the field of translational medicine. Baishideng Publishing Group Inc 2021-08-14 2021-08-14 /pmc/articles/PMC8384741/ /pubmed/34497429 http://dx.doi.org/10.3748/wjg.v27.i30.4963 Text en ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Review
Traub, Benno
Roth, Aileen
Kornmann, Marko
Knippschild, Uwe
Bischof, Joachim
Stress-activated kinases as therapeutic targets in pancreatic cancer
title Stress-activated kinases as therapeutic targets in pancreatic cancer
title_full Stress-activated kinases as therapeutic targets in pancreatic cancer
title_fullStr Stress-activated kinases as therapeutic targets in pancreatic cancer
title_full_unstemmed Stress-activated kinases as therapeutic targets in pancreatic cancer
title_short Stress-activated kinases as therapeutic targets in pancreatic cancer
title_sort stress-activated kinases as therapeutic targets in pancreatic cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384741/
https://www.ncbi.nlm.nih.gov/pubmed/34497429
http://dx.doi.org/10.3748/wjg.v27.i30.4963
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