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<p>Despite the initial response to androgen signaling therapy, most cases of prostate cancer (PCa) eventually relapse and remain incurable. The specific function of ADAR1 that governs PCa progression and specific inhibitors of ADAR are underexplored. In this study, we demonstrate that highly expressed ADAR1 is a crucial oncogenic target in PCa and develop an effective small-molecule ADAR1 inhibitor, ZYS-1, with marked antitumor efficacy and a favorable safety profile. Either genetic or pharmacological inhibition of ADAR1 dramatically suppressed PCa growth and metastasis and potentiated the antitumor immune response. Moreover, ZYS-1 can enhance the antitumor effect of immunotherapy. We also reveal that ADAR1 represses the translation of MTDH in an editing-dependent manner, which drives cell proliferation and invasion in PCa. Collectively, our findings suggest that ADAR1 is a druggable target in PCa and highlight the widespread applicability of ADAR1 inhibitors for a broad spectrum of malignancies.</p>

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Targeting ADAR1 with a small molecule for the treatment of prostate cancer

  • 期刊论文

  • 发表日期：

    2025年2月10日

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  • Xiao Wang,
  • Jiaxing Li,
  • Yasheng Zhu,
  • Hongtao Shen,
  • Jiayu Ding,
  • Ting Zeng,
  • Wenjian Min,
  • Shun-Qing Liang,
  • Lei Huang,
  • Zhongrui Shi,
  • Hao Shen,
  • Fei Huang,
  • Kai Yuan,
  • Wenbin Kuang,
  • Minghui Ji,
  • Chengliang Sun,
  • Yi Hou,
  • Liping Wang,
  • Weijiao Chen,
  • Yuzhang Jiang,
  • Haiping Hao,
  • Yibei Xiao,
  • Peng Yang

摘要

Despite the initial response to androgen signaling therapy, most cases of prostate cancer (PCa) eventually relapse and remain incurable. The specific function of ADAR1 that governs PCa progression and specific inhibitors of ADAR are underexplored. In this study, we demonstrate that highly expressed ADAR1 is a crucial oncogenic target in PCa and develop an effective small-molecule ADAR1 inhibitor, ZYS-1, with marked antitumor efficacy and a favorable safety profile. Either genetic or pharmacological inhibition of ADAR1 dramatically suppressed PCa growth and metastasis and potentiated the antitumor immune response. Moreover, ZYS-1 can enhance the antitumor effect of immunotherapy. We also reveal that ADAR1 represses the translation of MTDH in an editing-dependent manner, which drives cell proliferation and invasion in PCa. Collectively, our findings suggest that ADAR1 is a druggable target in PCa and highlight the widespread applicability of ADAR1 inhibitors for a broad spectrum of malignancies.