Preclinical models of prostate cancer - modelling androgen dependency and castration resistance in vitro, ex vivo and in vivo.
Journal
Nature reviews. Urology
ISSN: 1759-4820
Titre abrégé: Nat Rev Urol
Pays: England
ID NLM: 101500082
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
accepted:
20
01
2023
medline:
3
8
2023
pubmed:
15
2
2023
entrez:
14
2
2023
Statut:
ppublish
Résumé
Prostate cancer is well known to be dependent on the androgen receptor (AR) for growth and survival. Thus, AR is the main pharmacological target to treat this disease. However, after an initially positive response to AR-targeting therapies, prostate cancer will eventually evolve to castration-resistant prostate cancer, which is often lethal. Tumour growth was initially thought to become androgen-independent following treatments; however, results from molecular studies have shown that most resistance mechanisms involve the reactivation of AR. Consequently, tumour cells become resistant to castration - the blockade of testicular androgens - and not independent of AR per se. However, confusion still remains on how to properly define preclinical models of prostate cancer, including cell lines. Most cell lines were isolated from patients for cell culture after evolution of the tumour to castration-resistant prostate cancer, but not all of these cell lines are described as castration resistant. Moreover, castration refers to the blockade of testosterone production by the testes; thus, even the concept of "castration" in vitro is questionable. To ensure maximal transfer of knowledge from scientific research to the clinic, understanding the limitations and advantages of preclinical models, as well as how these models recapitulate cancer cell androgen dependency and can be used to study castration resistance mechanisms, is essential.
Identifiants
pubmed: 36788359
doi: 10.1038/s41585-023-00726-1
pii: 10.1038/s41585-023-00726-1
doi:
Substances chimiques
Androgens
0
Receptors, Androgen
0
Testosterone
3XMK78S47O
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
480-493Informations de copyright
© 2023. Springer Nature Limited.
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