Retinoid X Receptor agonists as selective modulators of the immune system for the treatment of cancer.
RXR agonists
Retinoid X receptor
Tumor immunity
Tumor microenvironment
Journal
Pharmacology & therapeutics
ISSN: 1879-016X
Titre abrégé: Pharmacol Ther
Pays: England
ID NLM: 7905840
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
01
05
2023
revised:
28
09
2023
accepted:
06
11
2023
pmc-release:
01
12
2024
medline:
4
12
2023
pubmed:
13
11
2023
entrez:
12
11
2023
Statut:
ppublish
Résumé
Upon heterodimerizing with other nuclear receptors, retinoid X receptors (RXR) act as ligand-dependent transcription factors, regulating transcription of critical signaling pathways that impact numerous hallmarks of cancer. By controlling both inflammation and immune responses, ligands that activate RXR can modulate the tumor microenvironment. Several small molecule agonists of these essential receptors have been synthesized. Historically, RXR agonists were tested for inhibition of growth in cancer cells, but more recent drug discovery programs screen new molecules for inhibition of inflammation or activation of immune cells. Bexarotene is the first successful example of an effective therapeutic that molecularly targets RXR; this drug was approved to treat cutaneous T cell lymphoma and is still used as a standard of care treatment for this disease. No additional RXR agonists have yet achieved FDA approval, but several promising novel compounds are being developed. In this review, we provide an overview of the multiple mechanisms by which RXR signaling regulates inflammation and tumor immunity. We also discuss the potential of RXR-dependent immune cell modulation for the treatment or prevention of cancer and concomitant challenges and opportunities.
Identifiants
pubmed: 37952906
pii: S0163-7258(23)00225-5
doi: 10.1016/j.pharmthera.2023.108561
pmc: PMC10704405
mid: NIHMS1945873
pii:
doi:
Substances chimiques
Retinoid X Receptors
0
Bexarotene
A61RXM4375
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
108561Subventions
Organisme : NCI NIH HHS
ID : R01 CA226690
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest KL & AL are named inventors on patent applications filed on RXR agonists owned by MSU and are founding scientists of Akeila Bio. Other authors have no potential conflicts to disclose.
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