The androgen receptor-targeted proteolysis targeting chimera and other alternative therapeutic choices in overcoming the resistance to androgen deprivation treatment in prostate cancer

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作者
Liuxun Li
Jiangli Xu
机构
[1] Faculty of Medical Sciences,Solid Tumour Target Discovery Laboratory, Translational and Clinical Research Institute
[2] Newcastle University Centre for Cancer,Department of Pharmacy
[3] Newcastle University,undefined
[4] No.921 Hospital of the Joint Logistics Support Force,undefined
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关键词
Androgen receptor; Prostate cancer; Androgen deprivation treatment; Resistance; Proteolysis targeting chimera;
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摘要
Androgen receptor (AR) plays a vital role in prostate cancer (PCa), including castration-resistant PCa, by retaining AR signalling. Androgen deprivation treatment (ADT) has been the standard treatment in the past decades. A great number of AR antagonists initially had been found effective in tumour remission; however, most PCa relapsed that caused by pre-translational resistance such as AR mutations to turn antagonist into agonist, and AR variants to bypass the androgen binding. Recently, several alternative therapeutic choices have been proposed. Among them, proteolysis targeting chimera (PROTAC) acts different from traditional drugs that usually function as inhibitors or antagonists, and it degrades oncogenic protein and does not disrupt the transcription of an oncogene. This review first discussed some essential mechanisms of ADT resistance, and then introduced the application of AR-targeted PROTAC in PCa cells, as well as other AR-targeted therapeutic choices.
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页码:352 / 363
页数:11
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