Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by early metastasis, late detection, and poor prognosis. Progress towards effective therapy has been slow despite significant efforts. Novel treatment approaches are desperately needed and autophagy, an evolutionary conse...

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Autores principales:	Alexander G. Raufi, Nicholas R. Liguori, Lindsey Carlsen, Cassandra Parker, Liz Hernandez Borrero, Shengliang Zhang, Xiaobing Tian, Anna Louie, Lanlan Zhou, Attila A. Seyhan, Wafik S. El-Deiry
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	autophagy pancreatic cancer MEK inhibitors ONC212 chloroquine Atg5 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/9e013afab8844e3382a6ba0292407a29
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spelling	oai:doaj.org-article:9e013afab8844e3382a6ba0292407a292021-12-01T19:21:48ZTherapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma1663-981210.3389/fphar.2021.751568https://doaj.org/article/9e013afab8844e3382a6ba0292407a292021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.751568/fullhttps://doaj.org/toc/1663-9812Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by early metastasis, late detection, and poor prognosis. Progress towards effective therapy has been slow despite significant efforts. Novel treatment approaches are desperately needed and autophagy, an evolutionary conserved process through which proteins and organelles are recycled for use as alternative energy sources, may represent one such target. Although incompletely understood, there is growing evidence suggesting that autophagy may play a role in PDAC carcinogenesis, metastasis, and survival. Early clinical trials involving autophagy inhibiting agents, either alone or in combination with chemotherapy, have been disappointing. Recently, evidence has demonstrated synergy between the MAPK pathway and autophagy inhibitors in PDAC, suggesting a promising therapeutic intervention. In addition, novel agents, such as ONC212, have preclinical activity in pancreatic cancer, in part through autophagy inhibition. We discuss autophagy in PDAC tumorigenesis, metabolism, modulation of the immune response, and preclinical and clinical data with selected autophagy modulators as therapeutics.Alexander G. RaufiAlexander G. RaufiAlexander G. RaufiAlexander G. RaufiNicholas R. LiguoriNicholas R. LiguoriLindsey CarlsenLindsey CarlsenLindsey CarlsenLindsey CarlsenCassandra ParkerCassandra ParkerLiz Hernandez BorreroLiz Hernandez BorreroShengliang ZhangShengliang ZhangShengliang ZhangShengliang ZhangXiaobing TianXiaobing TianXiaobing TianXiaobing TianAnna LouieAnna LouieLanlan ZhouLanlan ZhouLanlan ZhouLanlan ZhouAttila A. SeyhanAttila A. SeyhanAttila A. SeyhanAttila A. SeyhanWafik S. El-DeiryWafik S. El-DeiryWafik S. El-DeiryWafik S. El-DeiryWafik S. El-DeiryWafik S. El-DeiryFrontiers Media S.A.articleautophagypancreatic cancerMEK inhibitorsONC212chloroquineAtg5Therapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autophagy pancreatic cancer MEK inhibitors ONC212 chloroquine Atg5 Therapeutics. Pharmacology RM1-950
spellingShingle	autophagy pancreatic cancer MEK inhibitors ONC212 chloroquine Atg5 Therapeutics. Pharmacology RM1-950 Alexander G. Raufi Alexander G. Raufi Alexander G. Raufi Alexander G. Raufi Nicholas R. Liguori Nicholas R. Liguori Lindsey Carlsen Lindsey Carlsen Lindsey Carlsen Lindsey Carlsen Cassandra Parker Cassandra Parker Liz Hernandez Borrero Liz Hernandez Borrero Shengliang Zhang Shengliang Zhang Shengliang Zhang Shengliang Zhang Xiaobing Tian Xiaobing Tian Xiaobing Tian Xiaobing Tian Anna Louie Anna Louie Lanlan Zhou Lanlan Zhou Lanlan Zhou Lanlan Zhou Attila A. Seyhan Attila A. Seyhan Attila A. Seyhan Attila A. Seyhan Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma
description	Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by early metastasis, late detection, and poor prognosis. Progress towards effective therapy has been slow despite significant efforts. Novel treatment approaches are desperately needed and autophagy, an evolutionary conserved process through which proteins and organelles are recycled for use as alternative energy sources, may represent one such target. Although incompletely understood, there is growing evidence suggesting that autophagy may play a role in PDAC carcinogenesis, metastasis, and survival. Early clinical trials involving autophagy inhibiting agents, either alone or in combination with chemotherapy, have been disappointing. Recently, evidence has demonstrated synergy between the MAPK pathway and autophagy inhibitors in PDAC, suggesting a promising therapeutic intervention. In addition, novel agents, such as ONC212, have preclinical activity in pancreatic cancer, in part through autophagy inhibition. We discuss autophagy in PDAC tumorigenesis, metabolism, modulation of the immune response, and preclinical and clinical data with selected autophagy modulators as therapeutics.
format	article
author	Alexander G. Raufi Alexander G. Raufi Alexander G. Raufi Alexander G. Raufi Nicholas R. Liguori Nicholas R. Liguori Lindsey Carlsen Lindsey Carlsen Lindsey Carlsen Lindsey Carlsen Cassandra Parker Cassandra Parker Liz Hernandez Borrero Liz Hernandez Borrero Shengliang Zhang Shengliang Zhang Shengliang Zhang Shengliang Zhang Xiaobing Tian Xiaobing Tian Xiaobing Tian Xiaobing Tian Anna Louie Anna Louie Lanlan Zhou Lanlan Zhou Lanlan Zhou Lanlan Zhou Attila A. Seyhan Attila A. Seyhan Attila A. Seyhan Attila A. Seyhan Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry
author_facet	Alexander G. Raufi Alexander G. Raufi Alexander G. Raufi Alexander G. Raufi Nicholas R. Liguori Nicholas R. Liguori Lindsey Carlsen Lindsey Carlsen Lindsey Carlsen Lindsey Carlsen Cassandra Parker Cassandra Parker Liz Hernandez Borrero Liz Hernandez Borrero Shengliang Zhang Shengliang Zhang Shengliang Zhang Shengliang Zhang Xiaobing Tian Xiaobing Tian Xiaobing Tian Xiaobing Tian Anna Louie Anna Louie Lanlan Zhou Lanlan Zhou Lanlan Zhou Lanlan Zhou Attila A. Seyhan Attila A. Seyhan Attila A. Seyhan Attila A. Seyhan Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry Wafik S. El-Deiry
author_sort	Alexander G. Raufi
title	Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma
title_short	Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma
title_full	Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma
title_fullStr	Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma
title_full_unstemmed	Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma
title_sort	therapeutic targeting of autophagy in pancreatic ductal adenocarcinoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9e013afab8844e3382a6ba0292407a29
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Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma

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