LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential
| Autor: | Christopher S. Hong, Elder Jb, Zhang C, Chunzhang Yang, Zhengping Zhuang, Winson S. Ho |
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| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Programmed cell death Radiation-Sensitizing Agents DNA damage Drug Evaluation Preclinical Mitosis Antineoplastic Agents Apoptosis Review Biology Piperazines Neoplasms Animals Humans Protein Phosphatase 2 Enzyme Inhibitors Mitotic catastrophe Wnt Signaling Pathway Pharmacology Oncogene Proteins Tumor Suppressor Proteins Cell Cycle Tumor Protein Translationally-Controlled 1 Protein phosphatase 2 Cell cycle Bridged Bicyclo Compounds Heterocyclic Small molecule Oncology Drug Resistance Neoplasm Cancer cell Cancer research Molecular Medicine |
| Zdroj: | Cancer biologytherapy. 16(6) |
| ISSN: | 1555-8576 |
| Popis: | Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that plays a significant role in mitotic progression and cellular responses to DNA damage. While traditionally viewed as a tumor suppressor, inhibition of PP2A has recently come to attention as a novel therapeutic means of driving senescent cancer cells into mitosis and promoting cell death via mitotic catastrophe. These findings have been corroborated in numerous studies utilizing naturally produced compounds that selectively inhibit PP2A. To overcome the known human toxicities associated with these compounds, a water-soluble small molecule inhibitor, LB100, was recently developed to competitively inhibit the PP2A protein. This review summarizes the pre-clinical studies to date that have demonstrated the anti-cancer activity of LB100 via its chemo- and radio-sensitizing properties. These studies demonstrate the tremendous therapeutic potential of LB100 in a variety of cancer types. The results of an ongoing phase 1 trial are eagerly anticipated. |
| Databáze: | OpenAIRE |
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