The androgen receptor (AR) is a key driver of prostate cancer (PCa) and, as such, current mainstay treatments target this molecule. However, resistance commonly arises to these therapies and, therefore, additional targets must be evaluated to improve patient outcomes. Consequently, alternative approaches for indirectly targeting the AR are sought. AR crosstalk with other signalling pathways, including several protein kinase signalling cascades, has been identified as a potential route to combat therapy resistance. The casein kinase 1 (CK1) family of protein kinases phosphorylate a multitude of substrates, allowing them to regulate a diverse range of pathways from the cell cycle to DNA damage repair. As well as its role in several signalling pathways that are de-regulated in PCa, mutational data suggest its potential to promote prostate carcinogenesis. CK1α is one isoform predicted to regulate AR activity via phosphorylation and has been implicated in the progression of several other cancer types. In this review, we explore how the normal biological function of CK1 is de-regulated in cancer, the impact on signalling pathways and how this contributes towards prostate tumourigenesis, with a particular focus on the CK1α isoform as a novel therapeutic target for PCa.
雄激素受体（AR）是前列腺癌（PCa）的关键驱动因子，因此当前的主流治疗方法均以该分子为靶点。然而，这些疗法常出现耐药问题，故需评估其他靶点以改善患者预后。因此，研究者开始寻求间接靶向AR的替代策略。AR与其他信号通路（包括多种蛋白激酶信号级联）的交互作用已被确定为克服治疗耐药性的潜在途径。酪蛋白激酶1（CK1）蛋白激酶家族通过磷酸化多种底物，能够调控从细胞周期到DNA损伤修复的广泛通路。除在前列腺癌失调的多个信号通路中发挥作用外，突变数据还提示其可能促进前列腺癌发生。CK1α亚型被预测可通过磷酸化调控AR活性，并已在多种其他癌症类型的进展中被证实具有重要作用。本综述探讨了CK1在癌症中正常生物学功能的失调机制、其对信号通路的影响及其在前列腺肿瘤发生中的作用，特别聚焦于CK1α亚型作为前列腺癌新型治疗靶点的潜力。
肿瘤(癌症)患者之家