A FOXC2 inhibitor, MC-1-F2, as a therapeutic candidate for targeting EMT in castration-resistant prostate cancer
Bioorganic & Medicinal Chemistry Letters(2023)
摘要
Androgen deprivation therapy (ADT) is the major treatment option for advanced prostate cancer. However, prostate cancer can develop into androgen-independent castration-resistant prostate cancer (CRPC) which is resistant to ADT. An alternative treatment strategy for CRPC can be targeting the epithelial-mesenchymal transition (EMT). EMT is governed by a series of transcription factors of which forkhead box protein C2 (FOXC2) is a central mediator. Our previous research into the inhibition of FOXC2 in breast cancer cells lead to the discovery of MC-1-F2, the first direct inhibitor of FOXC2. In current study on CRPC, MC-1-F2 has shown a decrease in mesenchymal markers, inhibition of cancer stem cell (CSC) properties and decrease in invasive capabilities of CRPC cell lines. We have also demonstrated a synergistic effect between MC-1-F2 and docetaxel treatments, leading to a decrease in docetaxel dosage, suggesting the possible combination therapy of MC-1-F2 and docetaxel for the effective treatment of CRPC.
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关键词
foxc2 inhibitor,prostate cancer,castration-resistant
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