Cancer stemness serine-threonine kinases

Cancer stemness serine-threonine kinases (CSKs) are a functional group of enzymes that play a critical role in the maintenance, self-renewal, and survival of cancer stem cells (CSCs) [1, 4]. This group includes specific members such as STK33 and STK17A, which are often overexpressed in various malignancies and are responsible for phosphorylating and stabilizing key stemness transcription factors like Nanog and β-catenin [2, 3]. By regulating these pathways, CSKs contribute significantly to tumor heterogeneity, therapeutic resistance, and the ability of tumors to recur after conventional treatment [1, 4]. Therapeutic targeting of these kinases aims to deplete the CSC pool, thereby enhancing the efficacy of standard chemotherapies and reducing the risk of metastasis [1, 4]. Amcasertib (BBI-503) is a notable first-in-class small molecule inhibitor designed to target this group of kinases, showing potential in clinical trials for advanced solid tumors [2, 3]. The inhibition of these kinases leads to the downregulation of stemness markers and the sensitization of tumor cells to apoptotic stimuli [2, 5].

Other names

Cancer stemness kinasesCSC kinasesStemness-related kinasesCSKs

Inhibition of specific serine/threonine kinases (such as STK33 and STK17A) to disrupt the phosphorylation and stabilization of stemness-related transcription factors, including Nanog and β-catenin, thereby reducing the cancer stem cell population [2, 3].