Preclinical models of prostate cancer - modelling androgen dependency and castration resistance in vitro, ex vivo and in vivo.

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.

Nature reviews. Urology. 2023 Feb 14 [Epub ahead of print]

Lucas Germain, Camille Lafront, Virginie Paquette, Bertrand Neveu, Jean-Sébastien Paquette, Frédéric Pouliot, Étienne Audet-Walsh

Endocrinology - Nephrology Research Axis, CHU de Québec - Université Laval Research Center, Québec, QC, Canada., Centre de recherche sur le cancer de l'Université Laval, Québec, QC, Canada., Laboratoire de recherche et d'innovation en médecine de première ligne (ARIMED), Groupe de médecine de famille universitaire de Saint-Charles-Borromée, CISSS Lanaudière, Saint-Charles-Borromée, QC, Canada., Endocrinology - Nephrology Research Axis, CHU de Québec - Université Laval Research Center, Québec, QC, Canada. .