PBK, also known as PDZ-binding kinase or TOPK (T-lymphokine-activated killer-cell-originated protein kinase), is a serine/threonine protein kinase associated with the dual-specific mitogen-activated protein kinase (MAPKK) family. It plays crucial roles in mitosis and cell-cycle progression, especially in proliferative cells. PBK is involved in multiple signaling pathways such as MAPK, PI3K/PTEN/AKT, and NOTCH1, and its abnormal overexpression is associated with the development, progression, and metastasis of malignancies [2,3].

In ovarian cancer, overexpression of PBK contributes to olaparib resistance. Knockdown of PBK in olaparib-resistant SKOV3 cells sensitizes them to olaparib, and inhibition of PBK with a specific inhibitor enhances olaparib's therapeutic efficiency. Mechanistically, PBK directly interacts with TRIM37 to promote its phosphorylation and nuclear translocation, activating the NFκB pathway [1]. In cervical cancer, PBK is highly expressed and promotes cell proliferation, metastasis, and cisplatin resistance. The PBK inhibitor OTS514 can suppress these malignant phenotypes in vitro and in a xenograft model by targeting the ERK/c-Myc signaling pathway [4].

In conclusion, PBK is a key regulator in cell-cycle-related biological processes and is significantly associated with cancer-related diseases. Studies using gene-targeting methods in cell lines and in vivo models, such as those with PBK inhibitors or knockdown, have revealed its role in conferring drug resistance and promoting cancer progression, suggesting that PBK could be a potential therapeutic target for cancer treatment.