PBK/TOPK: A Therapeutic Target Worthy of Attention

Abstract

Accumulating evidence supports the role of PDZ-binding kinase (PBK)/T-lymphokine-activated killer-cell-originated protein kinase (TOPK) in mitosis and cell-cycle progression of mitotically active cells, especially proliferative malignant cells. PBK/TOPK was confirmed to be associated with the development, progression, and metastasis of malignancies. Therefore, it is a potential therapeutic target in cancer therapy. Many studies have been conducted to explore the clinical applicability of potent PBK/TOPK inhibitors. However, PBK/TOPK has also been shown to be overexpressed in normal proliferative cells, including sperm and neural precursor cells in the subventricular zone of the adult brain, as well as under pathological conditions, such as ischemic tissues, including the heart, brain, and kidney, and plays important roles in their physiological functions, including proliferation and self-renewal. Thus, more research is warranted to further our understanding of PBK/TOPK inhibitors before we can consider their applicability in clinical practice. In this study, we first review the findings, general features, and signaling mechanisms involved in the regulation of mitosis and cell cycle. We then review the functions of PBK/TOPK in pathological conditions, including tumors and ischemic conditions in the heart, brain, and kidney. Finally, we summarize the advances in potent and selective inhibitors and describe the potential use of PBK/TOPK inhibitors in clinical settings.