Abiraterone, a CYP17A1 inhibitor approved by the FDA, has been approved for the treatment of castration-resistant prostate cancer (CRPC)[1].
In vitro, Abiraterone (20 or 40μM; 72h) treatment significantly reduced mitochondrial respiration in T98G and U87MG-R cells[2]. The antiandrogen Abiraterone (0, 1, 5, 10 and 20μM; 72h) in combination with inhibitors of Polo-like kinase 1 synergistically kills CRPC cells[3].
In vivo, In an orthotopic brain tumor mouse model, co-administration of Abiraterone (10mg/kg; once every three days; i.p.) and Progesterone significantly curtailed the progression of implanted U87MG-R-luc GBM tumors[2]. The use of the small-molecule inhibitor Abiraterone (10mg/kg; 20 days; i.p.) to reduce testosterone synthesis significantly enhanced the antitumor activity of T cells in male mice and improved the efficacy of anti-PD-1 immunotherapy[4].
References:
[1] Lu D, Song Y, Yu Y, et al. KAT2A-mediated AR translocation into nucleus promotes abiraterone-resistance in castration-resistant prostate cancer. Cell Death Dis. 2021 Aug 12;12(8):787.
[2] Chen HC, Lin HY, Chiang YH, et al. Progesterone boosts abiraterone-driven target and NK cell therapies against glioblastoma. J Exp Clin Cancer Res. 2024 Aug 6;43(1):218.
[3] Patterson JC, Varkaris A, Croucher PJP, et al. Plk1 Inhibitors and Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling. Cancer Res. 2023 Jan 18;83(2):219-238.
[4] Zhang X, Cheng L, Gao C, et al. Androgen Signaling Contributes to Sex Differences in Cancer by Inhibiting NF-κB Activation in T Cells and Suppressing Antitumor Immunity. Cancer Res. 2023 Mar 15;83(6):906-921.
Abiraterone是一种FDA批准的CYP17A1抑制剂，已获批准用于去势抵抗性前列腺癌（CRPC）的治疗[1]。
在体外实验中，Abiraterone（20或40μM; 72小时）处理显著降低了T98G和U87MG-R细胞的线粒体呼吸[2]。抗雄激素Abiraterone（0, 1, 5, 10和20μM; 72小时）与Polo样激酶1抑制剂联合使用可协同杀死去势抵抗性前列腺癌细胞[3]。
在体内实验中，在原位脑肿瘤小鼠模型中，Abiraterone（10mg/kg; 每3天给药一次; 腹腔注射）与孕酮联合使用显著抑制了植入的U87MG-R-luc胶质母细胞瘤肿瘤的进展[2]。使用小分子抑制剂Abiraterone（10mg/kg; 20天; 腹腔注射）减少睾酮合成显著增强了雄性小鼠中T细胞的抗肿瘤活性，并提高了抗PD-1免疫疗法的疗效[4]。