Antagonism of the ATP-gated P2X7 receptor: a potential therapeutic strategy for cancer.
Antagonists
Cancer
Inflammation
P2X7 receptor
Purinergic receptors
Journal
Purinergic signalling
ISSN: 1573-9546
Titre abrégé: Purinergic Signal
Pays: Netherlands
ID NLM: 101250499
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
12
11
2020
accepted:
18
02
2021
pubmed:
18
3
2021
medline:
29
1
2022
entrez:
17
3
2021
Statut:
ppublish
Résumé
The P2X receptor 7 (P2X7R) is a plasma membrane receptor sensing extracellular ATP associated with a wide variety of cellular functions. It is most commonly expressed on immune cells and is highly upregulated in a number of human cancers where it can play a trophic role in tumorigenesis. Activation of this receptor leads to the formation of a non-selective cation channel, which has been associated with several cellular functions mediated by the PI3K/Akt pathway and protein kinases. Due to its broad range of functions, the receptor represents a potential therapeutic target for a number of cancers. This review describes the range of mechanisms associated with P2X7R activation in cancer settings and highlights the potential of targeted inhibition of P2X7R as a therapy. It also describes in detail a number of key P2X7R antagonists currently in pre-clinical and clinical development, including oxidised ATP, Brilliant Blue G (BBG), KN-62, KN-04, A740003, A438079, GSK1482160, CE-224535, JNJ-54175446, JNJ-55308942, and AZ10606120. Lastly, it summarises the in vivo studies and clinical trials associated with the use and development of these P2X7R antagonists in different disease contexts.
Identifiants
pubmed: 33728582
doi: 10.1007/s11302-021-09776-9
pii: 10.1007/s11302-021-09776-9
pmc: PMC8155177
doi:
Substances chimiques
Antineoplastic Agents
0
Purinergic P2X Receptor Antagonists
0
Receptors, Purinergic P2X7
0
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
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