Cargando…

Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma

The most frequent mutated oncogene family in the history of human cancer is the RAS gene family, including NRAS, HRAS, and, most importantly, KRAS. A hallmark of pancreatic cancer, recalcitrant cancer with a very low survival rate, is the prevalence of oncogenic mutations in the KRAS gene. Due to th...

Descripción completa

Detalles Bibliográficos
Autores principales: Hafezi, Shirin, Saber-Ayad, Maha, Abdel-Rahman, Wael M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508406/
https://www.ncbi.nlm.nih.gov/pubmed/34638560
http://dx.doi.org/10.3390/ijms221910219
_version_ 1784582089608265728
author Hafezi, Shirin
Saber-Ayad, Maha
Abdel-Rahman, Wael M.
author_facet Hafezi, Shirin
Saber-Ayad, Maha
Abdel-Rahman, Wael M.
author_sort Hafezi, Shirin
collection PubMed
description The most frequent mutated oncogene family in the history of human cancer is the RAS gene family, including NRAS, HRAS, and, most importantly, KRAS. A hallmark of pancreatic cancer, recalcitrant cancer with a very low survival rate, is the prevalence of oncogenic mutations in the KRAS gene. Due to this fact, studying the function of KRAS and the impact of its mutations on the tumor microenvironment (TME) is a priority for understanding pancreatic cancer progression and designing novel therapeutic strategies for the treatment of the dismal disease. Despite some recent enlightening studies, there is still a wide gap in our knowledge regarding the impact of KRAS mutations on different components of the pancreatic TME. In this review, we will present an updated summary of mutant KRAS role in the initiation, progression, and modulation of the TME of pancreatic ductal adenocarcinoma (PDAC). This review will highlight the intriguing link between diabetes mellitus and PDAC, as well as vitamin D as an adjuvant effective therapy via TME modulation of PDAC. We will also discuss different ongoing clinical trials that use KRAS oncogene signaling network as therapeutic targets.
format Online
Article
Text
id pubmed-8508406
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85084062021-10-13 Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma Hafezi, Shirin Saber-Ayad, Maha Abdel-Rahman, Wael M. Int J Mol Sci Review The most frequent mutated oncogene family in the history of human cancer is the RAS gene family, including NRAS, HRAS, and, most importantly, KRAS. A hallmark of pancreatic cancer, recalcitrant cancer with a very low survival rate, is the prevalence of oncogenic mutations in the KRAS gene. Due to this fact, studying the function of KRAS and the impact of its mutations on the tumor microenvironment (TME) is a priority for understanding pancreatic cancer progression and designing novel therapeutic strategies for the treatment of the dismal disease. Despite some recent enlightening studies, there is still a wide gap in our knowledge regarding the impact of KRAS mutations on different components of the pancreatic TME. In this review, we will present an updated summary of mutant KRAS role in the initiation, progression, and modulation of the TME of pancreatic ductal adenocarcinoma (PDAC). This review will highlight the intriguing link between diabetes mellitus and PDAC, as well as vitamin D as an adjuvant effective therapy via TME modulation of PDAC. We will also discuss different ongoing clinical trials that use KRAS oncogene signaling network as therapeutic targets. MDPI 2021-09-23 /pmc/articles/PMC8508406/ /pubmed/34638560 http://dx.doi.org/10.3390/ijms221910219 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hafezi, Shirin
Saber-Ayad, Maha
Abdel-Rahman, Wael M.
Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma
title Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma
title_full Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma
title_fullStr Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma
title_full_unstemmed Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma
title_short Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma
title_sort highlights on the role of kras mutations in reshaping the microenvironment of pancreatic adenocarcinoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508406/
https://www.ncbi.nlm.nih.gov/pubmed/34638560
http://dx.doi.org/10.3390/ijms221910219
work_keys_str_mv AT hafezishirin highlightsontheroleofkrasmutationsinreshapingthemicroenvironmentofpancreaticadenocarcinoma
AT saberayadmaha highlightsontheroleofkrasmutationsinreshapingthemicroenvironmentofpancreaticadenocarcinoma
AT abdelrahmanwaelm highlightsontheroleofkrasmutationsinreshapingthemicroenvironmentofpancreaticadenocarcinoma