A novel anti-androgen, Compound 30, suppresses castration-resistant and MDV3100-resistant prostate cancer growth in vitro and in vivo
Menée in vitro et in vivo, cette étude compare l'efficacité d'un nouveau composé anti-androgénique appelé Compound 30 avec celle du MVD3100 pour le traitement d'un cancer de la prostate résistant à la castration
Resistance to anti-androgen drugs, like MDV3100, occurs in patients with castration resistant prostate cancer (CRPC). Thus, preventing or treating anti-androgen resistance is a major clinical challenge. We identified a novel anti-androgen, Compound 30, and compared its efficacy to MDV3100. We found that Compound 30 inhibits AR activity in LNCaP cells, C4-2 cells, as well as MDV3100 resistant cell lines. Compared to MDV3100, Compound 30 treatment induces greater reduction in AR, PSA, and AR transcriptional activity, and prevents AR nuclear translocation, in AR-sensitive LNCaP cells. Compound 30 has anti-proliferative effects in LNCaP cells, in castrate-resistant C4-2 cells, and those resistant to MDV3100. Compound 30 was equally as effective as MDV3100 in reducing tumor volume and PSA in vivo. More importantly, Compound 30 is effective at inhibiting AR activity in MDV3100 resistant cell lines and significantly prevented tumor growth and PSA increases in mice bearing MDV3100 resistant xenografts. Together, our data show that Compound 30 strongly inhibited AR activity and suppressed castration-resistant LNCaP growth as well as MDV3100-resistant cell growth in vitro and in vivo. These data provide a pre-clinical proof-of-principle that Compound 30 could be a promising next generation anti-AR agent, especially in the context of anti-androgens resistant tumors.
http://mct.aacrjournals.org/content/early/2013/03/14/1535-7163.MCT-12-0798.abstract 2013