Development and Application of the PROTAC Technique in Castrate-resistant Prostate Cancer
10.13865/j.cnki.cjbmb.2025.03.1314
- VernacularTitle:蛋白质水解靶向嵌合体技术在去势抵抗性前列腺癌中的发展及应用
- Author:
Si-Jia WANG
1
;
Cheng XU
;
Wen-Min CHEN
Author Information
1. 沈阳药科大学生命科学与生物制药学院药学系,沈阳 110016;甘李药业股份有限公司,北京 101100
- Publication Type:Journal Article
- Keywords:
castrate resistant prostate cancer(CRPC);
androgen receptor(AR);
proteolysis targeting chimeras(PROTACs)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(5):653-663
- CountryChina
- Language:Chinese
-
Abstract:
Abnormal signaling in the androgen receptor(AR)signaling pathway is critical for prostate cancer development and progression,so inhibition of AR activity through androgen deprivation therapy(ADT)is an important means to control the development of prostate cancer in the early stage.However,most patients relapse and develop castrate-resistant prostate cancer(CRPC)within 6～20 months.Sur-gery and radiotherapy are still the major treatments for CRPC,but there are adverse effects such as urina-ry symptoms and sexual dysfunction.The first and second generatiosn of novel AR inhibitors can effec-tively treat CRPC.However,resistance to these chemicals is inevitable,and thus many patients may ex-perience recurrence.Resistance to AR inhibitors mainly consists of AR mutations,splice variant forma-tion and amplification,which have been shown to play an important role in CRPC.Also,aberrant activa-tion of cyclin dependent kinase(CDKs)and epigenetic alterations(e.g.histone modifications and DNA methylation)have been reported to be associated with prostate cancer progression.Proteolysis targeting chimeras(PROTACs)have unique advantages in CRPC therapy by virtue of their unique mechanism of action,ability to target non-druggable proteins,and specific binding to targets.In this review,we sum-marize the development of PROTAC technology for the treatment of CRPC by targeting different structural domains of AR,CDKs and epigenetic markers,and discuss the future prospects and challenges of PRO-TACs in the therapeutic field.
