Review of PP2A Tumor Biology and Antitumor Effects of PP2A Inhibitor LB100 in the Nervous System.

Abstract

Simple SummaryCentral and peripheral nervous system tumors represent a heterogenous group of neoplasms which often demonstrate resistance to treatment. Given that these tumors are often refractory to conventional therapy, novel pharmaceutical regimens are needed for successfully treating this pathology. One such therapeutic is the serine/threonine phosphatase inhibitor, LB100. LB100 is a water-soluble competitive protein phosphtase inhibitor that has demonstrated antitumor effects in preclinical and clinical trials. In this review, we aim to summarize current evidence demonstrating the efficacy of LB100 as an inhibitor of nervous system tumors. Furthermore, we review the involvement of the well-studied phosphatase, protein phosphatase 2A, in oncogenic cell signaling pathways, neurophysiology, and neurodevelopment.Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase implicated in a wide variety of regulatory cellular functions. PP2A is abundant in the mammalian nervous system, and dysregulation of its cellular functions is associated with myriad neurodegenerative disorders. Additionally, PP2A has oncologic implications, recently garnering attention and emerging as a therapeutic target because of the antitumor effects of a potent PP2A inhibitor, LB100. LB100 abrogation of PP2A is believed to exert its inhibitory effects on tumor progression through cellular chemo- and radiosensitization to adjuvant agents. An updated and unifying review of PP2A biology and inhibition with LB100 as a therapeutic strategy for targeting cancers of the nervous system is needed, as other reviews have mainly covered broader applications of LB100. In this review, we discuss the role of PP2A in normal cells and tumor cells of the nervous system. Furthermore, we summarize current evidence regarding the therapeutic potential of LB100 for treating solid tumors of the nervous system.