Stemness-associated serine-threonine kinases

Stemness-associated serine-threonine kinases (also referred to as cancer stemness kinases) represent a functional group of enzymes that are essential for the maintenance, self-renewal, and survival of cancer stem cells (CSCs). This group primarily includes kinases such as STK33, STK17A (DRAK1), STK38 (NDR1), and STK38L (NDR2), which are often upregulated in various malignancies and correlate with poor clinical outcomes. These kinases function by regulating the expression and activity of master stemness transcription factors, including Nanog, Oct4, and Sox2, thereby promoting a dedifferentiated, pluripotent state that facilitates tumor initiation, metastasis, and resistance to standard therapies. For instance, STK17A has been shown to phosphorylate beta-catenin to enhance Wnt signaling, while STK33 is critical for the survival of KRAS-dependent cancer cells. The most prominent therapeutic agent targeting this group is amcasertib (BBI-503), a first-in-class multi-kinase inhibitor designed to deplete the CSC population. Clinical development of such inhibitors focuses on overcoming chemoresistance and preventing disease recurrence in advanced solid tumors, although challenges such as gastrointestinal toxicity and the complexity of stemness signaling pathways remain.

Other names

Cancer stemness kinasesCSC kinasesSerine/threonine stemness kinasesStemness kinases

Inhibition of multiple serine-threonine kinases (including STK33, STK17A, STK38, and STK38L) to downregulate the expression of stemness transcription factors such as Nanog, Oct4, and Sox2, thereby inhibiting the survival and self-renewal of cancer stem cells.