Xie Kangzhe, Tan Keely, Naylor Matthew J
Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine & Health, University of Sydney, Sydney, NSW, Australia.
Front Oncol. 2022 Apr 25;12:854151. doi: 10.3389/fonc.2022.854151. eCollection 2022.
Prostate cancer is the second most diagnosed cancer among men worldwide. Androgen deprivation therapy, the most common targeted therapeutic option, is circumvented as prostate cancer progresses from androgen dependent to castrate-resistant disease. Whilst the nuclear receptor transcription factor, androgen receptor, drives the growth of prostate tumor during initial stage of the disease, androgen resistance is associated with poorly differentiated prostate cancer. In the recent years, increased research has highlighted the aberrant transcriptional activities of a small number of transcription factors. Along with androgen receptors, dysregulation of these transcription factors contributes to both the poorly differentiated phenotypes of prostate cancer cells and the initiation and progression of prostate carcinoma. As master regulators of cell fate decisions, these transcription factors may provide opportunity for the development of novel therapeutic targets for the management of prostate cancer. Whilst some transcriptional regulators have previously been notoriously difficult to directly target, technological advances offer potential for the indirect therapeutic targeting of these transcription factors and the capacity to reprogram cancer cell phenotype. This mini review will discuss how recent advances in our understanding of transcriptional regulators and material science pave the way to utilize these regulatory molecules as therapeutic targets in prostate cancer.
前列腺癌是全球男性中第二大最常被诊断出的癌症。随着前列腺癌从雄激素依赖型发展为去势抵抗性疾病，最常见的靶向治疗选择——雄激素剥夺疗法就会失效。虽然核受体转录因子雄激素受体在疾病初期驱动前列腺肿瘤的生长，但雄激素抵抗与低分化前列腺癌有关。近年来，越来越多的研究突出了少数转录因子的异常转录活性。除了雄激素受体外，这些转录因子的失调既导致前列腺癌细胞的低分化表型，也促成前列腺癌的发生和发展。作为细胞命运决定的主要调节因子，这些转录因子可能为开发用于治疗前列腺癌的新型治疗靶点提供机会。虽然一些转录调节因子以前一直 notoriously difficult to directly target，但技术进步为间接治疗靶向这些转录因子以及重编程癌细胞表型提供了潜力。本综述将讨论我们对转录调节因子和材料科学的最新认识进展如何为将这些调节分子用作前列腺癌的治疗靶点铺平道路。
