Androgen-Independent Prostate Cancer Is Sensitive to CDC42-PAK7 Kinase Inhibition

Hyunho Han, Cheol Keun Park, Young Deuk Choi, Nam Hoon Cho, Jongsoo Lee, Kang Su Cho

Research output: Contribution to journalArticlepeer-review


Prostate cancer is a common form of cancer in men, and androgen-deprivation therapy (ADT) is often used as a first-line treatment. However, some patients develop resistance to ADT, and their disease is called castration-resistant prostate cancer (CRPC). Identifying potential therapeutic targets for this aggressive subtype of prostate cancer is crucial. In this study, we show that statins can selectively inhibit the growth of these CRPC tumors that have lost their androgen receptor (AR) and have overexpressed the RNA-binding protein QKI. We found that the repression of microRNA-200 by QKI overexpression promotes the rise of AR-low mesenchymal-like CRPC cells. Using in silico drug/gene perturbation combined screening, we discovered that QKI-overexpressing cancer cells are selectively vulnerable to CDC42-PAK7 inhibition by statins. We also confirmed that PAK7 overexpression is present in prostate cancer that coexists with hyperlipidemia. Our results demonstrate a previously unseen mechanism of action for statins in these QKI-expressing AR-lost CRPCs. This may explain the clinical benefits of the drug and support the development of a biology-driven drug-repurposing clinical trial. This is an important finding that could help improve treatment options for patients with this aggressive form of prostate cancer.

Original languageEnglish
Article number101
Issue number1
Publication statusPublished - 2023 Jan

Bibliographical note

Funding Information:
This research was supported by a grant of the Republic of Korea Health Technology R&D Project through the Republic of Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C1186000022) (PI: H.H.).

Publisher Copyright:
© 2022 by the authors.

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)


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