Prolactin receptor signaling: A novel target for cancer treatment - Exploring anti-PRLR signaling strategies.
PrlR
antagonist
antibody-drug conjugate
immunotherapy
small molecule inhibitor
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2022
2022
Historique:
received:
30
11
2022
accepted:
22
12
2022
entrez:
30
1
2023
pubmed:
31
1
2023
medline:
1
2
2023
Statut:
epublish
Résumé
Prolactin (PRL) is a peptide hormone mainly secreted from the anterior pituitary gland. PRL is reported to play a role in pregnancy, mammary gland development, immune modulation, reproduction, and differentiation of islet cells. PRL binds to its receptor PRLR, which belongs to a superfamily of the class I cytokine receptor that has no intrinsic kinase activity. In canonical signaling, PRL binding to PRLR induces downstream signaling including JAK-STAT, AKT and MAPK pathways. This leads to increased cell proliferation, stemness, migration, apoptosis inhibition, and resistance to chemotherapy. PRL-signaling is upregulated in numerous hormone-dependent cancers including breast, prostate, ovarian, and endometrial cancer. However, more recently, the pathway has been reported to play a tumor-promoting role in other cancer types such as colon, pancreas, and hepatocellular cancers. Hence, the signaling pathway is an attractive target for drug development with blockade of the receptor being a potential therapeutic approach. Different strategies have been developed to target this receptor including modification of PRL peptides (Del1-9-G129R-hPRL, G129R-Prl), growth hormone receptor/prolactin receptor bispecific antibody antagonist, neutralizing antibody LFA102, an antibody-drug conjugate (ABBV-176) of the humanized antibody h16f (PR-1594804) and pyrrolobenzodiazepine dimer, a bispecific antibody targeting both PRLR and CD3, an
Identifiants
pubmed: 36714582
doi: 10.3389/fendo.2022.1112987
pmc: PMC9880166
doi:
Substances chimiques
Prolactin
9002-62-4
Receptors, Prolactin
0
Carrier Proteins
0
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1112987Subventions
Organisme : NCI NIH HHS
ID : P30 CA168524
Pays : United States
Informations de copyright
Copyright © 2023 Standing, Dandawate and Anant.
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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