Ion Channels Orchestrate Pancreatic Ductal Adenocarcinoma Progression and Therapy.
fibrosis
immune cells
ion channels
pancreatic ductal adenocarcinoma
therapy
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2020
2020
Historique:
received:
23
07
2020
accepted:
30
10
2020
entrez:
12
4
2021
pubmed:
13
4
2021
medline:
13
4
2021
Statut:
epublish
Résumé
Pancreatic ductal adenocarcinoma is a devastating disease with a dismal prognosis. Therapeutic interventions are largely ineffective. A better understanding of the pathophysiology is required. Ion channels contribute substantially to the "hallmarks of cancer." Their expression is dysregulated in cancer, and they are "misused" to drive cancer progression, but the underlying mechanisms are unclear. Ion channels are located in the cell membrane at the interface between the intracellular and extracellular space. They sense and modify the tumor microenvironment which in itself is a driver of PDAC aggressiveness. Ion channels detect, for example, locally altered proton and electrolyte concentrations or mechanical stimuli and transduce signals triggered by these microenvironmental cues through association with intracellular signaling cascades. While these concepts have been firmly established for other cancers, evidence has emerged only recently that ion channels are drivers of PDAC aggressiveness. Particularly, they appear to contribute to two of the characteristic PDAC features: the massive fibrosis of the tumor stroma (desmoplasia) and the efficient immune evasion. Our critical review of the literature clearly shows that there is still a remarkable lack of knowledge with respect to the contribution of ion channels to these two typical PDAC properties. Yet, we can draw parallels from ion channel research in other fibrotic and inflammatory diseases. Evidence is accumulating that pancreatic stellate cells express the same "profibrotic" ion channels. Similarly, it is at least in part known which major ion channels are expressed in those innate and adaptive immune cells that populate the PDAC microenvironment. We explore potential therapeutic avenues derived thereof. Since drugs targeting PDAC-relevant ion channels are already in clinical use, we propose to repurpose those in PDAC. The quest for ion channel targets is both motivated and complicated by the fact that some of the relevant channels, for example, K
Identifiants
pubmed: 33841132
doi: 10.3389/fphar.2020.586599
pii: 586599
pmc: PMC8025202
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
586599Informations de copyright
Copyright © 2021 Hofschröer, Najder, Rugi, Bouazzi, Cozzolino, Arcangeli, Panyi and Schwab.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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