T-lymphokine-activated killer cell-originated protein kinase (TOPK)

T-lymphokine-activated killer cell-originated protein kinase (TOPK, also known as PDZ-binding kinase, PBK) is a serine/threonine kinase classified within the mitogen-activated protein kinase kinase (MAPKK)-like enzyme family. It is highly expressed in proliferating cells and particularly overexpressed in a broad spectrum of solid and hematologic cancers, including breast, lung, colon, skin, ovarian, glioma, renal, and others. TOPK is minimally expressed in differentiated adult tissues, making it a promising biomarker and therapeutic target for cancer. Its biological roles include promoting cell cycle progression, proliferation, and survival, suppressing apoptosis, and modulating the MAPK pathway. Overexpression of TOPK commonly correlates with tumor aggressiveness, metastatic potential, and poor patient prognosis across multiple cancer types. Several small molecule TOPK inhibitors (such as OTS514, 3-Deoxysappanchalcone, and HI-TOPK-032) have been developed, showing efficacy in experimental models both alone and in synergy with conventional chemotherapeutics, but clinical trials are still pending. Elevated TOPK expression may also identify drug-resistant cancers and serve as a target for overcoming resistance mechanisms. The selective targeting of TOPK is being actively explored for both diagnostic and therapeutic applications in oncology.

Other names

PDZ-binding kinase (PBK)T-LAK cell-originated protein kinase (TOPK)T-lymphokine-activated killer cell-originated protein kinasePBK/TOPK

Kinase inhibition (direct inhibition of TOPK activity by small molecules like OTS514, 3-DSC, HI-TOPK-032) Enhanced chemosensitization (combination with doxorubicin, cisplatin, temozolomide, or sorafenib leads to increased cancer cell death) Downregulation leads to suppressed cell proliferation, migration, invasion, and colony formation