{"title":"利用新型抗雄激素抑制剂 ADA-308 攻克腺癌和恩扎鲁胺耐药性前列腺癌。","authors":"Shaghayegh Nouruzi, Fraser Johnson, Sahil Kumar, Olena Sivak, Nakisa Tabrizian, Milla Koistinaho, Anu Muona, Amina Zoubeidi","doi":"10.3892/or.2024.8791","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>in vitro</i> assessments of AR activity and cell proliferation, alongside <i>in vivo</i> 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 <i>in vitro</i>. Furthermore, ADA‑308 demonstrated notable efficacy <i>in vivo</i>, 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.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"52 4","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332584/pdf/","citationCount":"0","resultStr":"{\"title\":\"Targeting adenocarcinoma and enzalutamide‑resistant prostate cancer using the novel anti‑androgen inhibitor ADA‑308.\",\"authors\":\"Shaghayegh Nouruzi, Fraser Johnson, Sahil Kumar, Olena Sivak, Nakisa Tabrizian, Milla Koistinaho, Anu Muona, Amina Zoubeidi\",\"doi\":\"10.3892/or.2024.8791\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>in vitro</i> assessments of AR activity and cell proliferation, alongside <i>in vivo</i> 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 <i>in vitro</i>. Furthermore, ADA‑308 demonstrated notable efficacy <i>in vivo</i>, 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.</p>\",\"PeriodicalId\":19527,\"journal\":{\"name\":\"Oncology reports\",\"volume\":\"52 4\",\"pages\":\"\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332584/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oncology reports\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3892/or.2024.8791\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncology reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3892/or.2024.8791","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/12 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
前列腺癌(PCa)是全球男性因癌症死亡的主要原因。PCa通常会对标准的雄激素剥夺疗法和雄激素受体(AR)通路抑制剂(如恩扎鲁胺(ENZ))产生耐药性。因此,迫切需要针对这种疾病开发新的治疗策略。ADA-308 的疗效通过 AR 活性和细胞增殖的体外评估以及体内研究进行了评估。ADA-308 对 AR 敏感的腺癌细胞系和 ENZ 抗性 PCa 细胞系都有很强的抑制作用,是一种很有前途的候选药物。研究结果表明,ADA-308 能有效阻断 AR 活性,包括其核定位,并抑制体外细胞增殖。此外,ADA-308 在体内也表现出了显著的疗效,在 ENZ 抗性模型中产生了强大的抗肿瘤反应。这些发现确立了ADA-308作为一种强效AR抑制剂的作用,它能克服AR靶向疗法的耐药性,并突显了它作为一种新型治疗方法在晚期PCa治疗中的潜力。
Targeting adenocarcinoma and enzalutamide‑resistant prostate cancer using the novel anti‑androgen inhibitor ADA‑308.
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.
期刊介绍:
Oncology Reports is a monthly, peer-reviewed journal devoted to the publication of high quality original studies and reviews concerning a broad and comprehensive view of fundamental and applied research in oncology, focusing on carcinogenesis, metastasis and epidemiology.