LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential
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 senes...
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| Veröffentlicht in: | Cancer biology & therapy 2015-01, Vol.16 (6), p.821-833 |
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| creator | Hong, Christopher S Ho, Winson Zhang, Chao Yang, Chunzhang Elder, J Bradley Zhuang, Zhengping |
| description | 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. |
| doi_str_mv | 10.1080/15384047.2015.1040961 |
| format | Article |
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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.</description><identifier>ISSN: 1538-4047</identifier><identifier>EISSN: 1555-8576</identifier><identifier>DOI: 10.1080/15384047.2015.1040961</identifier><identifier>PMID: 25897893</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Bridged Bicyclo Compounds, Heterocyclic - pharmacology ; cell cycle ; Cell Cycle - drug effects ; chemosensitization ; Drug Evaluation, Preclinical ; Drug Resistance, Neoplasm ; Enzyme Inhibitors - pharmacology ; Humans ; Mitosis - drug effects ; Mitosis - genetics ; mitotic catastrophe ; Neoplasms - drug therapy ; Neoplasms - genetics ; Neoplasms - metabolism ; Oncogene Proteins - antagonists & inhibitors ; Oncogene Proteins - genetics ; Oncogene Proteins - metabolism ; Piperazines - pharmacology ; Protein Phosphatase 2 - antagonists & inhibitors ; Protein Phosphatase 2 - genetics ; Protein Phosphatase 2 - metabolism ; protein phosphatase 2A ; Radiation-Sensitizing Agents - pharmacology ; radiosensitizationreview ; Review ; small molecule inhibitor ; Tumor Suppressor Proteins - antagonists & inhibitors ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Wnt Signaling Pathway - drug effects</subject><ispartof>Cancer biology & therapy, 2015-01, Vol.16 (6), p.821-833</ispartof><rights>2015 Taylor and Francis Group, LLC 2015</rights><rights>2015 Taylor and Francis Group, LLC 2015 Taylor and Francis Group, LLC</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-c6e1b9be620df17d721a2601ae65ef8bba13c0d0df61a2ae809a8a1ae217c4dc3</citedby><cites>FETCH-LOGICAL-c468t-c6e1b9be620df17d721a2601ae65ef8bba13c0d0df61a2ae809a8a1ae217c4dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623051/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623051/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25897893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hong, Christopher S</creatorcontrib><creatorcontrib>Ho, Winson</creatorcontrib><creatorcontrib>Zhang, Chao</creatorcontrib><creatorcontrib>Yang, Chunzhang</creatorcontrib><creatorcontrib>Elder, J Bradley</creatorcontrib><creatorcontrib>Zhuang, Zhengping</creatorcontrib><title>LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential</title><title>Cancer biology & therapy</title><addtitle>Cancer Biol Ther</addtitle><description>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.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</subject><subject>cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>chemosensitization</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drug Resistance, Neoplasm</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Humans</subject><subject>Mitosis - drug effects</subject><subject>Mitosis - genetics</subject><subject>mitotic catastrophe</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Oncogene Proteins - antagonists & inhibitors</subject><subject>Oncogene Proteins - genetics</subject><subject>Oncogene Proteins - metabolism</subject><subject>Piperazines - pharmacology</subject><subject>Protein Phosphatase 2 - antagonists & inhibitors</subject><subject>Protein Phosphatase 2 - genetics</subject><subject>Protein Phosphatase 2 - metabolism</subject><subject>protein phosphatase 2A</subject><subject>Radiation-Sensitizing Agents - pharmacology</subject><subject>radiosensitizationreview</subject><subject>Review</subject><subject>small molecule inhibitor</subject><subject>Tumor Suppressor Proteins - antagonists & inhibitors</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Wnt Signaling Pathway - drug effects</subject><issn>1538-4047</issn><issn>1555-8576</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKxDAUhoMo3h9ByQPYMUmbNN2IF7zBgLPQnRBO09RG0mZIOg769LbMjOjGVQ75b_AhdELJhBJJzilPZUayfMII5cNXRgpBt9A-5Zwnkudie7xTmYymPXQQ4zshLGei2EV7jMsil0W6j16n15SQMww4tuAcbr0zeuEMtl1jS9v7gH2NZzN2hZe2b_Dc96brsW5M6xMMXYUDVNYn0XTR9vbLdm9rjwV3hHZqcNEcr99D9HJ3-3zzkEyf7h9vrqaJzoTsEy0MLYvSCEaqmuZVzigwQSgYwU0tyxJoqkk1iGIQwEhSgIRBZjTXWaXTQ3Sx6p0vytZUelgP4NQ82BbCp_Jg1V-ls4168x8qEywlnA4FfFWgg48xmPonS4kacasNbjXiVmvcQ-709_BPasN3MFyuDLarfWhh6YOrVA-fzoc6QKdtVOn_G98BuZDY</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Hong, Christopher S</creator><creator>Ho, Winson</creator><creator>Zhang, Chao</creator><creator>Yang, Chunzhang</creator><creator>Elder, J Bradley</creator><creator>Zhuang, Zhengping</creator><general>Taylor & Francis</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20150101</creationdate><title>LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential</title><author>Hong, Christopher S ; Ho, Winson ; Zhang, Chao ; Yang, Chunzhang ; Elder, J Bradley ; Zhuang, Zhengping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-c6e1b9be620df17d721a2601ae65ef8bba13c0d0df61a2ae809a8a1ae217c4dc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</topic><topic>cell cycle</topic><topic>Cell Cycle - drug effects</topic><topic>chemosensitization</topic><topic>Drug Evaluation, Preclinical</topic><topic>Drug Resistance, Neoplasm</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Humans</topic><topic>Mitosis - drug effects</topic><topic>Mitosis - genetics</topic><topic>mitotic catastrophe</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - metabolism</topic><topic>Oncogene Proteins - antagonists & inhibitors</topic><topic>Oncogene Proteins - genetics</topic><topic>Oncogene Proteins - metabolism</topic><topic>Piperazines - pharmacology</topic><topic>Protein Phosphatase 2 - antagonists & inhibitors</topic><topic>Protein Phosphatase 2 - genetics</topic><topic>Protein Phosphatase 2 - metabolism</topic><topic>protein phosphatase 2A</topic><topic>Radiation-Sensitizing Agents - pharmacology</topic><topic>radiosensitizationreview</topic><topic>Review</topic><topic>small molecule inhibitor</topic><topic>Tumor Suppressor Proteins - antagonists & inhibitors</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Wnt Signaling Pathway - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hong, Christopher S</creatorcontrib><creatorcontrib>Ho, Winson</creatorcontrib><creatorcontrib>Zhang, Chao</creatorcontrib><creatorcontrib>Yang, Chunzhang</creatorcontrib><creatorcontrib>Elder, J Bradley</creatorcontrib><creatorcontrib>Zhuang, Zhengping</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer biology & therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hong, Christopher S</au><au>Ho, Winson</au><au>Zhang, Chao</au><au>Yang, Chunzhang</au><au>Elder, J Bradley</au><au>Zhuang, Zhengping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential</atitle><jtitle>Cancer biology & therapy</jtitle><addtitle>Cancer Biol Ther</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>16</volume><issue>6</issue><spage>821</spage><epage>833</epage><pages>821-833</pages><issn>1538-4047</issn><eissn>1555-8576</eissn><abstract>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. 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| subjects | Animals Antineoplastic Agents - pharmacology Apoptosis - drug effects Bridged Bicyclo Compounds, Heterocyclic - pharmacology cell cycle Cell Cycle - drug effects chemosensitization Drug Evaluation, Preclinical Drug Resistance, Neoplasm Enzyme Inhibitors - pharmacology Humans Mitosis - drug effects Mitosis - genetics mitotic catastrophe Neoplasms - drug therapy Neoplasms - genetics Neoplasms - metabolism Oncogene Proteins - antagonists & inhibitors Oncogene Proteins - genetics Oncogene Proteins - metabolism Piperazines - pharmacology Protein Phosphatase 2 - antagonists & inhibitors Protein Phosphatase 2 - genetics Protein Phosphatase 2 - metabolism protein phosphatase 2A Radiation-Sensitizing Agents - pharmacology radiosensitizationreview Review small molecule inhibitor Tumor Suppressor Proteins - antagonists & inhibitors Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Wnt Signaling Pathway - drug effects |
| title | LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential |
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