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Review | Open Access

Targeting PP2A for cancer therapeutic modulation

Halle Ronk, Jared S. Rosenblum, Timothy Kung, Zhengping Zhuang( )
Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
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Abstract

Protein phosphatases play essential roles as negative regulators of kinases and signaling cascades involved in cytoskeletal organization. Protein phosphatase 2A (PP2A) is highly conserved and is the predominant serine/threonine phosphatase in the nervous system, constituting more than 70% of all neuronal phosphatases. PP2A is involved in diverse regulatory functions, including cell cycle progression, apoptosis, and DNA repair. Although PP2A has historically been identified as a tumor suppressor, inhibition of PP2A has paradoxically demonstrated potential as a therapeutic target for various cancers. LB100, a water-soluble, small-molecule competitive inhibitor of PP2A, has shown particular promise as a chemo- and radio-sensitizing agent. Preclinical success has led to a profusion of clinical trials on LB100 adjuvant therapies, including a phase Ⅰ trial in extensive-stage small-cell lung cancer, a phase Ⅰ/Ⅱ trial in myelodysplastic syndrome, a phase Ⅱ trial in recurrent glioblastoma, and a completed phase Ⅰ trial assessing the safety of LB100 and docetaxel in various relapsed solid tumors. Herein, we review the development of LB100, the role of PP2A in cancer biology, and recent advances in targeting PP2A inhibition in immunotherapy.

Keywords

immunotherapycolorectal cancerglioblastomaclinical trialsChemo-sensitizationLB100protein phosphatase 2APP2A inhibitionradio-sensitizationsmall molecule inhibitor

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Cancer Biology & Medicine
Volume 19 Issue 10,
October 2022
Pages 1428-1439
DOI: 10.20892/j.issn.2095-3941.2022.0330
Cite this article:
Ronk H, Rosenblum JS, Kung T, et al. Targeting PP2A for cancer therapeutic modulation. Cancer Biology & Medicine, 2022, 19(10): 1428-1439. https://doi.org/10.20892/j.issn.2095-3941.2022.0330

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Received: 15 June 2022
Accepted: 26 August 2022
Published: 03 November 2022
©2022 Cancer Biology & Medicine.

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