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Investigational New Drugs
Erschienen in:

27.01.2025 | Research

Synergistic antitumor effect of MK-1775 and CUDC-907 against prostate cancer

verfasst von: Saisai Ma, Yichen Xu, Minmin Liu, Shuaida Wu, Ye Zhang, Hongyan Xia, Ji Lu, Yang Zhan

Erschienen in: Investigational New Drugs | Ausgabe 1/2025

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Abstract

Due to the emergence of drug resistance, androgen receptor (AR)-targeted drugs still pose great challenges in the treatment of prostate cancer, and it is urgent to explore an innovative therapeutic strategy. MK-1775, a highly selective WEE1 inhibitor, is shown to have favorable therapeutic benefits in several solid tumor models. Recent evidence suggests that the combination of MK-1775 with DNA-damaging agents could lead to enhanced antitumor efficacy. Here, our results demonstrate that MK-1775 alone could indeed inhibit proliferation and induce apoptosis in prostate cancer. Moreover, the combination of MK-1775 and a dual PI3K and HDAC inhibitor, CUDC-907, can synergistically inhibit cell proliferation and dramatically induces apoptosis in prostate cancer cells. This effect is partially mediated by DNA damage, resulting from the downregulation of DNA damage response (DDR) proteins such as CDK, CHK, and RRM1/2. Notably, the combination of MK-1775 and CUDC-907 leads to significant antitumor effects in vivo. Our findings provide a strong basis for a promising combination strategy against prostate cancer.

Graphical Abstract

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Metadaten
Titel
Synergistic antitumor effect of MK-1775 and CUDC-907 against prostate cancer
verfasst von
Saisai Ma
Yichen Xu
Minmin Liu
Shuaida Wu
Ye Zhang
Hongyan Xia
Ji Lu
Yang Zhan
Publikationsdatum
27.01.2025
Verlag
Springer US
Erschienen in
Investigational New Drugs / Ausgabe 1/2025
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-024-01490-8

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