PP2A Activation as a Senotherapeutic in Neuroblastoma

Background/Objectives: Therapy-induced senescence (TIS), while initially growth-suppressive, may promote tumor recurrence through the persistence of senescent cells and the senescence-associated secretory phenotype (SASP). Topotecan, a topoisomerase inhibitor and a key component in the treatment of neuroblastoma (NBL), is known to lead to TIS. Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that has been linked to cellular senescence. PP2A is downregulated in NBL, primarily through upregulation of its endogenous inhibitors. We have previously shown that a novel small molecule, ATUX-1215, activates PP2A in NBL cells.