Targeting PP2A for cancer therapeutic modulation
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 neu...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
China Anti-Cancer Association
2022-10-01
|
| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | https://www.cancerbiomed.org/content/19/10/1428 |
| _version_ | 1828094430810210304 |
|---|---|
| author | Halle Ronk Jared S. Rosenblum Timothy Kung Zhengping Zhuang |
| author_facet | Halle Ronk Jared S. Rosenblum Timothy Kung Zhengping Zhuang |
| author_sort | Halle Ronk |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T06:58:37Z |
| format | Article |
| id | doaj.art-1be5051d52924dcb9bdfbfbf386153f3 |
| institution | Directory Open Access Journal |
| issn | 2095-3941 |
| language | English |
| last_indexed | 2024-04-11T06:58:37Z |
| publishDate | 2022-10-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj.art-1be5051d52924dcb9bdfbfbf386153f32022-12-22T04:38:54ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412022-10-0119101428143910.20892/j.issn.2095-3941.2022.0330Targeting PP2A for cancer therapeutic modulationHalle Ronk0Jared S. Rosenblum1Timothy Kung2Zhengping Zhuang3Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USANeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USANeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USANeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAProtein 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.https://www.cancerbiomed.org/content/19/10/1428chemo-sensitizationclinical trialscolorectal cancerglioblastomaimmunotherapylb100protein phosphatase 2app2a inhibitionradio-sensitizationsmall molecule inhibitor |
| spellingShingle | Halle Ronk Jared S. Rosenblum Timothy Kung Zhengping Zhuang Targeting PP2A for cancer therapeutic modulation Cancer Biology & Medicine chemo-sensitization clinical trials colorectal cancer glioblastoma immunotherapy lb100 protein phosphatase 2a pp2a inhibition radio-sensitization small molecule inhibitor |
| title | Targeting PP2A for cancer therapeutic modulation |
| title_full | Targeting PP2A for cancer therapeutic modulation |
| title_fullStr | Targeting PP2A for cancer therapeutic modulation |
| title_full_unstemmed | Targeting PP2A for cancer therapeutic modulation |
| title_short | Targeting PP2A for cancer therapeutic modulation |
| title_sort | targeting pp2a for cancer therapeutic modulation |
| topic | chemo-sensitization clinical trials colorectal cancer glioblastoma immunotherapy lb100 protein phosphatase 2a pp2a inhibition radio-sensitization small molecule inhibitor |
| url | https://www.cancerbiomed.org/content/19/10/1428 |
| work_keys_str_mv | AT halleronk targetingpp2aforcancertherapeuticmodulation AT jaredsrosenblum targetingpp2aforcancertherapeuticmodulation AT timothykung targetingpp2aforcancertherapeuticmodulation AT zhengpingzhuang targetingpp2aforcancertherapeuticmodulation |