Multiple serine-threonine stemness kinases

Multiple serine-threonine stemness kinases refer to a group of enzymes that are essential for the maintenance and self-renewal of cancer stem cells (CSCs). These kinases regulate the expression and activity of master stemness transcription factors, including Nanog, OCT4, and SOX2, which allow CSCs to survive conventional chemotherapy and drive tumor recurrence and metastasis [1, 12]. Amcasertib (BBI-503) is a first-in-class, orally available small molecule designed to target these kinases [4, 15]. By inhibiting this group of enzymes, the drug disrupts the signaling pathways that sustain the stem-cell-like properties of cancer cells, potentially leading to tumor regression and prevention of relapse [16, 18]. Clinical trials have explored its efficacy in various advanced solid tumors, including colorectal, head and neck, and hepatocellular carcinomas, often in combination with standard-of-care agents [2, 15, 20]. Targeting these kinases represents a novel approach in oncology, as it specifically addresses the subpopulation of cells that are typically resistant to traditional cytotoxic treatments [16]. However, the exact identity of all kinases within this group has not been fully elucidated, presenting a challenge for precise molecular characterization [16, 19]. Despite this, the inhibition of these pathways has shown signs of anti-cancer activity and manageable safety profiles in early-phase clinical studies [15, 24].

Other names

Stemness kinasesCancer stemness-associated kinasesCancer stem cell kinasesCSC kinases

Inhibition of multiple serine-threonine kinases involved in cancer stemness pathways, leading to the downregulation of stemness factors such as Nanog, OCT4, and SOX2, and the suppression of cancer stem cell self-renewal and survival.