Tumor Microenvironment Features and Chemoresistance in Pancreatic Ductal Adenocarcinoma: Insights into Targeting Physicochemical Barriers and Metabolism as Therapeutic Approaches.
acidic pH
chemoresistance
desmoplasia
extracellular matrix
hypoxia
metabolism
pancreatic ductal adenocarcinoma
treatment
tumor microenvironment
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
06 Dec 2021
06 Dec 2021
Historique:
received:
26
10
2021
revised:
26
11
2021
accepted:
01
12
2021
entrez:
10
12
2021
pubmed:
11
12
2021
medline:
11
12
2021
Statut:
epublish
Résumé
Currently, the median overall survival of PDAC patients rarely exceeds 1 year and has an overall 5-year survival rate of about 9%. These numbers are anticipated to worsen in the future due to the lack of understanding of the factors involved in its strong chemoresistance. Chemotherapy remains the only treatment option for most PDAC patients; however, the available therapeutic strategies are insufficient. The factors involved in chemoresistance include the development of a desmoplastic stroma which reprograms cellular metabolism, and both contribute to an impaired response to therapy. PDAC stroma is composed of immune cells, endothelial cells, and cancer-associated fibroblasts embedded in a prominent, dense extracellular matrix associated with areas of hypoxia and acidic extracellular pH. While multiple gene mutations are involved in PDAC initiation, this desmoplastic stroma plays an important role in driving progression, metastasis, and chemoresistance. Elucidating the mechanisms underlying PDAC resistance are a prerequisite for designing novel approaches to increase patient survival. In this review, we provide an overview of the stromal features and how they contribute to the chemoresistance in PDAC treatment. By highlighting new paradigms in the role of the stromal compartment in PDAC therapy, we hope to stimulate new concepts aimed at improving patient outcomes.
Identifiants
pubmed: 34885243
pii: cancers13236135
doi: 10.3390/cancers13236135
pmc: PMC8657427
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : European Marie Skłodowska-Curie Innovative Training Network
ID : 813834; H2020-MSCA-ITN-2018
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