PDF(Pubmed)
Abstract：
Prostate cancer (PCa) is the leading cause of cancer‑related death among men worldwide. PCa often develops resistance to standard androgen deprivation therapy and androgen receptor (AR) pathway inhibitors, such as enzalutamide (ENZ). Therefore, there is an urgent need to develop novel therapeutic strategies for this disease. The efficacy of ADA‑308 was evaluated through in vitro assessments of AR activity and cell proliferation, alongside in vivo studies. ADA‑308 has emerged as a promising candidate, demonstrating potent inhibition of AR‑sensitive adenocarcinoma as well as ENZ‑resistant PCa cell lines. The results of the study revealed that ADA‑308 effectively blocked AR activity, including its nuclear localization, and inhibited cell proliferation in vitro. Furthermore, ADA‑308 demonstrated notable efficacy in vivo, with a robust antitumor response in ENZ‑resistant models. These findings establish the role of ADA‑308 as a potent AR inhibitor that overcomes resistance to AR‑targeted therapies and highlights its potential as a novel therapeutic approach in advanced PCa management.
摘要：
前列腺癌（PCa）是全球男性癌症相关死亡的主要原因。PCa通常对标准雄激素剥夺疗法和雄激素受体（AR）途径抑制剂产生耐药性，例如恩扎鲁他胺(ENZ)。因此,迫切需要开发新的治疗策略。通过体外评估AR活性和细胞增殖来评估ADA-308的功效，除了体内研究。ADA-308已经成为一个有前途的候选人，证明了对AR敏感性腺癌和ENZ抗性PCa细胞系的有效抑制。研究结果表明，ADA-308有效地阻断了AR活动，包括它的核本地化，并在体外抑制细胞增殖。此外，ADA-308在体内表现出显著的疗效，在抗ENZ模型中具有强大的抗肿瘤反应。这些发现确立了ADA-308作为一种有效的AR抑制剂的作用，克服了对AR靶向治疗的耐药性，并突出了其作为先进PCa管理中一种新型治疗方法的潜力。
