Casein Kinase 1α—A Target for Prostate Cancer Therapy?

Simple Summary Prostate cancer (PCa) is the most common cancer in males in the UK, resulting in more than 12,000 deaths per year in the UK. A large proportion of patients stop responding to currently available treatments; consequently, identifying alternative treatment options is key to prolonging the life of these men and improving survival rates. Protein kinases regulate signalling pathways, which are often dysregulated in cancer, leading to tumour growth. Additionally, kinase driven phosphorylation regulates androgen receptor activity, which is a key driver of PCa. Understanding how these signalling pathways contribute towards PCa is critical in the development of novel treatment options. The kinase, casein kinase 1 alpha (CK1α), has potential as a PCa therapeutic. Here we describe the current literature supporting this hypothesis and identify where further research is needed to fully understand the functional role and therapeutic potential of CK1α in PCa. Abstract 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.