Targeting adenocarcinoma and enzalutamide‑resistant prostate cancer using the novel anti‑androgen inhibitor ADA‑308

使用新型抗雄激素抑制剂 ADA-308 靶向治疗腺癌和恩杂鲁胺耐药前列腺癌

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作者:Shaghayegh Nouruzi #, Fraser Johnson #, Sahil Kumar, Olena Sivak, Nakisa Tabrizian, Milla Koistinaho, Anu Muona, Amina Zoubeidi

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.

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