Oncogenic <i>KRAS</i>-Induced Feedback Inflammatory Signaling in Pancreatic Cancer: An Overview and New Therapeutic Opportunities

Pancreatic ductal adenocarcinoma (PDAC) remains highly refractory to treatment. While the <i>KRAS</i> oncogene is present in almost all PDAC cases and accounts for many of the malignant feats of PDAC, targeting KRAS or its canonical, direct effector cascades remains unsuccessful in patie...

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Autores principales:	Sapana Bansod, Paarth B. Dodhiawala, Kian-Huat Lim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	inflammation stroma pancreatic cancer IRAK4 TPL2 TAK1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5d817c7138c64e199ef506aadd7b6506
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spelling	oai:doaj.org-article:5d817c7138c64e199ef506aadd7b65062021-11-11T15:33:39ZOncogenic <i>KRAS</i>-Induced Feedback Inflammatory Signaling in Pancreatic Cancer: An Overview and New Therapeutic Opportunities10.3390/cancers132154812072-6694https://doaj.org/article/5d817c7138c64e199ef506aadd7b65062021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5481https://doaj.org/toc/2072-6694Pancreatic ductal adenocarcinoma (PDAC) remains highly refractory to treatment. While the <i>KRAS</i> oncogene is present in almost all PDAC cases and accounts for many of the malignant feats of PDAC, targeting KRAS or its canonical, direct effector cascades remains unsuccessful in patients. The recalcitrant nature of PDAC is also heavily influenced by its highly fibro-inflammatory tumor microenvironment (TME), which comprises an acellular extracellular matrix and various types of non-neoplastic cells including fibroblasts, immune cells, and adipocytes, underscoring the critical need to delineate the bidirectional signaling interplay between PDAC cells and the TME in order to develop novel therapeutic strategies. The impact of tumor-cell KRAS signaling on various cell types in the TME has been well covered by several reviews. In this article, we critically reviewed evidence, including work from our group, on how the feedback inflammatory signals from the TME impact and synergize with oncogenic KRAS signaling in PDAC cells, ultimately augmenting their malignant behavior. We discussed past and ongoing clinical trials that target key inflammatory pathways in PDAC and highlight lessons to be learned from outcomes. Lastly, we provided our perspective on the future of developing therapeutic strategies for PDAC through understanding the breadth and complexity of KRAS and the inflammatory signaling network.Sapana BansodPaarth B. DodhiawalaKian-Huat LimMDPI AGarticleinflammationstromapancreatic cancerIRAK4TPL2TAK1Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5481, p 5481 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	inflammation stroma pancreatic cancer IRAK4 TPL2 TAK1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	inflammation stroma pancreatic cancer IRAK4 TPL2 TAK1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Sapana Bansod Paarth B. Dodhiawala Kian-Huat Lim Oncogenic <i>KRAS</i>-Induced Feedback Inflammatory Signaling in Pancreatic Cancer: An Overview and New Therapeutic Opportunities
description	Pancreatic ductal adenocarcinoma (PDAC) remains highly refractory to treatment. While the <i>KRAS</i> oncogene is present in almost all PDAC cases and accounts for many of the malignant feats of PDAC, targeting KRAS or its canonical, direct effector cascades remains unsuccessful in patients. The recalcitrant nature of PDAC is also heavily influenced by its highly fibro-inflammatory tumor microenvironment (TME), which comprises an acellular extracellular matrix and various types of non-neoplastic cells including fibroblasts, immune cells, and adipocytes, underscoring the critical need to delineate the bidirectional signaling interplay between PDAC cells and the TME in order to develop novel therapeutic strategies. The impact of tumor-cell KRAS signaling on various cell types in the TME has been well covered by several reviews. In this article, we critically reviewed evidence, including work from our group, on how the feedback inflammatory signals from the TME impact and synergize with oncogenic KRAS signaling in PDAC cells, ultimately augmenting their malignant behavior. We discussed past and ongoing clinical trials that target key inflammatory pathways in PDAC and highlight lessons to be learned from outcomes. Lastly, we provided our perspective on the future of developing therapeutic strategies for PDAC through understanding the breadth and complexity of KRAS and the inflammatory signaling network.
format	article
author	Sapana Bansod Paarth B. Dodhiawala Kian-Huat Lim
author_facet	Sapana Bansod Paarth B. Dodhiawala Kian-Huat Lim
author_sort	Sapana Bansod
title	Oncogenic <i>KRAS</i>-Induced Feedback Inflammatory Signaling in Pancreatic Cancer: An Overview and New Therapeutic Opportunities
title_short	Oncogenic <i>KRAS</i>-Induced Feedback Inflammatory Signaling in Pancreatic Cancer: An Overview and New Therapeutic Opportunities
title_full	Oncogenic <i>KRAS</i>-Induced Feedback Inflammatory Signaling in Pancreatic Cancer: An Overview and New Therapeutic Opportunities
title_fullStr	Oncogenic <i>KRAS</i>-Induced Feedback Inflammatory Signaling in Pancreatic Cancer: An Overview and New Therapeutic Opportunities
title_full_unstemmed	Oncogenic <i>KRAS</i>-Induced Feedback Inflammatory Signaling in Pancreatic Cancer: An Overview and New Therapeutic Opportunities
title_sort	oncogenic <i>kras</i>-induced feedback inflammatory signaling in pancreatic cancer: an overview and new therapeutic opportunities
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5d817c7138c64e199ef506aadd7b6506
work_keys_str_mv	AT sapanabansod oncogenicikrasiinducedfeedbackinflammatorysignalinginpancreaticcanceranoverviewandnewtherapeuticopportunities AT paarthbdodhiawala oncogenicikrasiinducedfeedbackinflammatorysignalinginpancreaticcanceranoverviewandnewtherapeuticopportunities AT kianhuatlim oncogenicikrasiinducedfeedbackinflammatorysignalinginpancreaticcanceranoverviewandnewtherapeuticopportunities
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Oncogenic <i>KRAS</i>-Induced Feedback Inflammatory Signaling in Pancreatic Cancer: An Overview and New Therapeutic Opportunities

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