The Extracellular Matrix in Pancreatic Cancer: Description of a Complex Network and Promising Therapeutic Options.
cancer-associated fibroblasts
extracellular matrix
matrix remodeling
solid stress
stiffness
stroma
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
03 Sep 2021
03 Sep 2021
Historique:
received:
04
08
2021
revised:
30
08
2021
accepted:
31
08
2021
entrez:
10
9
2021
pubmed:
11
9
2021
medline:
11
9
2021
Statut:
epublish
Résumé
The stroma is a relevant player in driving and supporting the progression of pancreatic ductal adenocarcinoma (PDAC), and a large body of evidence highlights its role in hindering the efficacy of current therapies. In fact, the dense extracellular matrix (ECM) characterizing this tumor acts as a natural physical barrier, impairing drug penetration. Consequently, all of the approaches combining stroma-targeting and anticancer therapy constitute an appealing option for improving drug penetration. Several strategies have been adopted in order to target the PDAC stroma, such as the depletion of ECM components and the targeting of cancer-associated fibroblasts (CAFs), which are responsible for the increased matrix deposition in cancer. Additionally, the leaky and collapsing blood vessels characterizing the tumor might be normalized, thus restoring blood perfusion and allowing drug penetration. Even though many stroma-targeting strategies have reported disappointing results in clinical trials, the ECM offers a wide range of potential therapeutic targets that are now being investigated. The dense ECM might be bypassed by implementing nanoparticle-based systems or by using mesenchymal stem cells as drug carriers. The present review aims to provide an overview of the principal mechanisms involved in the ECM remodeling and of new promising therapeutic strategies for PDAC.
Identifiants
pubmed: 34503252
pii: cancers13174442
doi: 10.3390/cancers13174442
pmc: PMC8430646
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : AIRC 5 x 1000
ID : 22737
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