High-throughput screens identify HSP90 inhibitors as potent therapeutics that target inter-related growth and survival pathways in advanced prostate cancer
The development of new treatments for castrate resistant prostate cancer (CRPC) must address such challenges as intrinsic tumor heterogeneity and phenotypic plasticity. Combined PTEN/ TP53 alterations represent a major genotype of CRPC (25–30%) and are associated with poor outcomes. Using tumor-deri...
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| creator | Jansson, Keith H. Tucker, John B. Stahl, Lauren E. Simmons, John K. Fuller, Caitlyn Beshiri, Michael L. Agarwal, Supreet Fang, Lei Hynes, Paul G. Alilin, Aian Neil Lake, Ross Abbey, Yasmine C. Cawley, Jacob Tice, Caitlin M. Yin, JuanJuan McKnight, Crystal Klummp-Thomas, Carleen Zhang, Xiaohu Guha, Rajarshi Hoover, Shelley Simpson, R. Mark Nguyen, Holly M. Corey, Eva Thomas, Craig J. Proia, David A. Kelly, Kathleen |
| description | The development of new treatments for castrate resistant prostate cancer (CRPC) must address such challenges as intrinsic tumor heterogeneity and phenotypic plasticity. Combined
PTEN/
TP53 alterations represent a major genotype of CRPC (25–30%) and are associated with poor outcomes. Using tumor-derived, castration-resistant
Pten/Tp53
null luminal prostate cells for comprehensive, high-throughput, mechanism-based screening, we identified several vulnerabilities among >1900 compounds, including inhibitors of: PI3K/AKT/mTOR, the proteasome, the cell cycle, heat shock proteins, DNA repair, NFκB, MAPK, and epigenetic modifiers. HSP90 inhibitors were one of the most active compound classes in the screen and have clinical potential for use in drug combinations to enhance efficacy and delay the development of resistance. To inform future design of rational drug combinations, we tested ganetespib, a potent second-generation HSP90 inhibitor, as a single agent in multiple CRPC genotypes and phenotypes. Ganetespib decreased growth of endogenous
Pten/Tp53
null tumors, confirming therapeutic activity
in situ
. Fifteen human CRPC LuCaP PDX-derived organoid models were assayed for responses to 110 drugs, and HSP90 inhibitors (ganetespib and onalespib) were among the select group of drugs (75% of models) at high potency (IC50 |
| doi_str_mv | 10.1038/s41598-018-35417-0 |
| format | Article |
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PTEN/
TP53 alterations represent a major genotype of CRPC (25–30%) and are associated with poor outcomes. Using tumor-derived, castration-resistant
Pten/Tp53
null luminal prostate cells for comprehensive, high-throughput, mechanism-based screening, we identified several vulnerabilities among >1900 compounds, including inhibitors of: PI3K/AKT/mTOR, the proteasome, the cell cycle, heat shock proteins, DNA repair, NFκB, MAPK, and epigenetic modifiers. HSP90 inhibitors were one of the most active compound classes in the screen and have clinical potential for use in drug combinations to enhance efficacy and delay the development of resistance. To inform future design of rational drug combinations, we tested ganetespib, a potent second-generation HSP90 inhibitor, as a single agent in multiple CRPC genotypes and phenotypes. Ganetespib decreased growth of endogenous
Pten/Tp53
null tumors, confirming therapeutic activity
in situ
. Fifteen human CRPC LuCaP PDX-derived organoid models were assayed for responses to 110 drugs, and HSP90 inhibitors (ganetespib and onalespib) were among the select group of drugs (<10%) that demonstrated broad activity (>75% of models) at high potency (IC50 <1 µM). Ganetespib inhibits multiple targets, including AR and PI3K pathways, which regulate mutually compensatory growth and survival signals in some forms of CRPC. Combined with castration, ganetespib displayed deeper PDX tumor regressions and delayed castration resistance relative to either monotherapy. In all, comprehensive data from near-patient models presents novel contexts for HSP90 inhibition in multiple CRPC genotypes and phenotypes, expands upon HSP90 inhibitors as simultaneous inhibitors of oncogenic signaling and resistance mechanisms, and suggests utility for combined HSP90/AR inhibition in CRPC.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-35417-0</identifier><identifier>PMID: 30467317</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>1-Phosphatidylinositol 3-kinase ; 13 ; 13/106 ; 631/67/589/466 ; 631/67/70 ; 64 ; AKT protein ; Castration ; Cell cycle ; DNA repair ; Drug development ; Epigenetics ; Genotypes ; Heat shock proteins ; Hsp90 protein ; Humanities and Social Sciences ; MAP kinase ; multidisciplinary ; NF-κB protein ; Organoids ; p53 Protein ; Phenotypes ; Phenotypic plasticity ; Prostate cancer ; Proteasomes ; PTEN protein ; Science ; Science (multidisciplinary) ; TOR protein ; Tumors</subject><ispartof>Scientific reports, 2018-11, Vol.8 (1), p.17239-13, Article 17239</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-299db332db617dcca65415eca0042d87c2f585fb914defd2d61e6cad991d1cf43</citedby><cites>FETCH-LOGICAL-c474t-299db332db617dcca65415eca0042d87c2f585fb914defd2d61e6cad991d1cf43</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/PMC6250716/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250716/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30467317$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jansson, Keith H.</creatorcontrib><creatorcontrib>Tucker, John B.</creatorcontrib><creatorcontrib>Stahl, Lauren E.</creatorcontrib><creatorcontrib>Simmons, John K.</creatorcontrib><creatorcontrib>Fuller, Caitlyn</creatorcontrib><creatorcontrib>Beshiri, Michael L.</creatorcontrib><creatorcontrib>Agarwal, Supreet</creatorcontrib><creatorcontrib>Fang, Lei</creatorcontrib><creatorcontrib>Hynes, Paul G.</creatorcontrib><creatorcontrib>Alilin, Aian Neil</creatorcontrib><creatorcontrib>Lake, Ross</creatorcontrib><creatorcontrib>Abbey, Yasmine C.</creatorcontrib><creatorcontrib>Cawley, Jacob</creatorcontrib><creatorcontrib>Tice, Caitlin M.</creatorcontrib><creatorcontrib>Yin, JuanJuan</creatorcontrib><creatorcontrib>McKnight, Crystal</creatorcontrib><creatorcontrib>Klummp-Thomas, Carleen</creatorcontrib><creatorcontrib>Zhang, Xiaohu</creatorcontrib><creatorcontrib>Guha, Rajarshi</creatorcontrib><creatorcontrib>Hoover, Shelley</creatorcontrib><creatorcontrib>Simpson, R. Mark</creatorcontrib><creatorcontrib>Nguyen, Holly M.</creatorcontrib><creatorcontrib>Corey, Eva</creatorcontrib><creatorcontrib>Thomas, Craig J.</creatorcontrib><creatorcontrib>Proia, David A.</creatorcontrib><creatorcontrib>Kelly, Kathleen</creatorcontrib><title>High-throughput screens identify HSP90 inhibitors as potent therapeutics that target inter-related growth and survival pathways in advanced prostate cancer</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The development of new treatments for castrate resistant prostate cancer (CRPC) must address such challenges as intrinsic tumor heterogeneity and phenotypic plasticity. Combined
PTEN/
TP53 alterations represent a major genotype of CRPC (25–30%) and are associated with poor outcomes. Using tumor-derived, castration-resistant
Pten/Tp53
null luminal prostate cells for comprehensive, high-throughput, mechanism-based screening, we identified several vulnerabilities among >1900 compounds, including inhibitors of: PI3K/AKT/mTOR, the proteasome, the cell cycle, heat shock proteins, DNA repair, NFκB, MAPK, and epigenetic modifiers. HSP90 inhibitors were one of the most active compound classes in the screen and have clinical potential for use in drug combinations to enhance efficacy and delay the development of resistance. To inform future design of rational drug combinations, we tested ganetespib, a potent second-generation HSP90 inhibitor, as a single agent in multiple CRPC genotypes and phenotypes. Ganetespib decreased growth of endogenous
Pten/Tp53
null tumors, confirming therapeutic activity
in situ
. Fifteen human CRPC LuCaP PDX-derived organoid models were assayed for responses to 110 drugs, and HSP90 inhibitors (ganetespib and onalespib) were among the select group of drugs (<10%) that demonstrated broad activity (>75% of models) at high potency (IC50 <1 µM). Ganetespib inhibits multiple targets, including AR and PI3K pathways, which regulate mutually compensatory growth and survival signals in some forms of CRPC. Combined with castration, ganetespib displayed deeper PDX tumor regressions and delayed castration resistance relative to either monotherapy. In all, comprehensive data from near-patient models presents novel contexts for HSP90 inhibition in multiple CRPC genotypes and phenotypes, expands upon HSP90 inhibitors as simultaneous inhibitors of oncogenic signaling and resistance mechanisms, and suggests utility for combined HSP90/AR inhibition in CRPC.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>13</subject><subject>13/106</subject><subject>631/67/589/466</subject><subject>631/67/70</subject><subject>64</subject><subject>AKT protein</subject><subject>Castration</subject><subject>Cell cycle</subject><subject>DNA repair</subject><subject>Drug development</subject><subject>Epigenetics</subject><subject>Genotypes</subject><subject>Heat shock proteins</subject><subject>Hsp90 protein</subject><subject>Humanities and Social Sciences</subject><subject>MAP kinase</subject><subject>multidisciplinary</subject><subject>NF-κB protein</subject><subject>Organoids</subject><subject>p53 Protein</subject><subject>Phenotypes</subject><subject>Phenotypic plasticity</subject><subject>Prostate cancer</subject><subject>Proteasomes</subject><subject>PTEN protein</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>TOR protein</subject><subject>Tumors</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc9u1DAQxiMEolXpC3BAlrhwSfG_OPEFCVWFRaoEEnC2HNtJXGXtYDtb7bPwssx2Sykc8MUez2--8firqpcEXxDMureZk0Z2NSZdzRpO2ho_qU4p5k1NGaVPH51PqvOcbzCshkpO5PPqhGEuWkba0-rnxo9TXaYU13Fa1oKySc6FjLx1ofhhjzZfv0iMfJh870tMGemMllggi8rkkl7cWrzJEGi40Wl0BejiUp3crIuzaEzxtkxIB4vymnZ-p2e06DLd6j30CUjbnQ4GwCXFXKAEmUOcXlTPBj1nd36_n1XfP1x9u9zU158_frp8f10b3vJSUyltzxi1vSCtNUYL-I_GGY0xp7ZrDR2arhl6Sbh1g6VWECeMtlISS8zA2Vn17qi7rP3WWQOjJT2rJfmtTnsVtVd_Z4Kf1Bh3StAGt0SAwJt7gRR_rC4XtfXZuHnWwcU1K0pYywWRjQT09T_oTVxTgPEOlJDgp-iAokfKwI_k5IaHxxCsDvaro_0KcHVnv8JQ9OrxGA8lv80GgB2BDKkwuvSn939kfwEozb_u</recordid><startdate>20181122</startdate><enddate>20181122</enddate><creator>Jansson, Keith H.</creator><creator>Tucker, John B.</creator><creator>Stahl, Lauren E.</creator><creator>Simmons, John K.</creator><creator>Fuller, Caitlyn</creator><creator>Beshiri, Michael L.</creator><creator>Agarwal, Supreet</creator><creator>Fang, Lei</creator><creator>Hynes, Paul G.</creator><creator>Alilin, Aian Neil</creator><creator>Lake, Ross</creator><creator>Abbey, Yasmine C.</creator><creator>Cawley, Jacob</creator><creator>Tice, Caitlin M.</creator><creator>Yin, JuanJuan</creator><creator>McKnight, Crystal</creator><creator>Klummp-Thomas, Carleen</creator><creator>Zhang, Xiaohu</creator><creator>Guha, Rajarshi</creator><creator>Hoover, Shelley</creator><creator>Simpson, R. Mark</creator><creator>Nguyen, Holly M.</creator><creator>Corey, Eva</creator><creator>Thomas, Craig J.</creator><creator>Proia, David A.</creator><creator>Kelly, Kathleen</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20181122</creationdate><title>High-throughput screens identify HSP90 inhibitors as potent therapeutics that target inter-related growth and survival pathways in advanced prostate cancer</title><author>Jansson, Keith H. ; Tucker, John B. ; Stahl, Lauren E. ; Simmons, John K. ; Fuller, Caitlyn ; Beshiri, Michael L. ; Agarwal, Supreet ; Fang, Lei ; Hynes, Paul G. ; Alilin, Aian Neil ; Lake, Ross ; Abbey, Yasmine C. ; Cawley, Jacob ; Tice, Caitlin M. ; Yin, JuanJuan ; McKnight, Crystal ; Klummp-Thomas, Carleen ; Zhang, Xiaohu ; Guha, Rajarshi ; Hoover, Shelley ; Simpson, R. Mark ; Nguyen, Holly M. ; Corey, Eva ; Thomas, Craig J. ; Proia, David A. ; Kelly, Kathleen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-299db332db617dcca65415eca0042d87c2f585fb914defd2d61e6cad991d1cf43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>13</topic><topic>13/106</topic><topic>631/67/589/466</topic><topic>631/67/70</topic><topic>64</topic><topic>AKT protein</topic><topic>Castration</topic><topic>Cell cycle</topic><topic>DNA repair</topic><topic>Drug development</topic><topic>Epigenetics</topic><topic>Genotypes</topic><topic>Heat shock proteins</topic><topic>Hsp90 protein</topic><topic>Humanities and Social Sciences</topic><topic>MAP kinase</topic><topic>multidisciplinary</topic><topic>NF-κB protein</topic><topic>Organoids</topic><topic>p53 Protein</topic><topic>Phenotypes</topic><topic>Phenotypic plasticity</topic><topic>Prostate cancer</topic><topic>Proteasomes</topic><topic>PTEN protein</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>TOR protein</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jansson, Keith H.</creatorcontrib><creatorcontrib>Tucker, John B.</creatorcontrib><creatorcontrib>Stahl, Lauren E.</creatorcontrib><creatorcontrib>Simmons, John K.</creatorcontrib><creatorcontrib>Fuller, Caitlyn</creatorcontrib><creatorcontrib>Beshiri, Michael L.</creatorcontrib><creatorcontrib>Agarwal, Supreet</creatorcontrib><creatorcontrib>Fang, Lei</creatorcontrib><creatorcontrib>Hynes, Paul G.</creatorcontrib><creatorcontrib>Alilin, Aian Neil</creatorcontrib><creatorcontrib>Lake, Ross</creatorcontrib><creatorcontrib>Abbey, Yasmine C.</creatorcontrib><creatorcontrib>Cawley, Jacob</creatorcontrib><creatorcontrib>Tice, Caitlin M.</creatorcontrib><creatorcontrib>Yin, JuanJuan</creatorcontrib><creatorcontrib>McKnight, Crystal</creatorcontrib><creatorcontrib>Klummp-Thomas, Carleen</creatorcontrib><creatorcontrib>Zhang, Xiaohu</creatorcontrib><creatorcontrib>Guha, Rajarshi</creatorcontrib><creatorcontrib>Hoover, Shelley</creatorcontrib><creatorcontrib>Simpson, R. Mark</creatorcontrib><creatorcontrib>Nguyen, Holly M.</creatorcontrib><creatorcontrib>Corey, Eva</creatorcontrib><creatorcontrib>Thomas, Craig J.</creatorcontrib><creatorcontrib>Proia, David A.</creatorcontrib><creatorcontrib>Kelly, Kathleen</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jansson, Keith H.</au><au>Tucker, John B.</au><au>Stahl, Lauren E.</au><au>Simmons, John K.</au><au>Fuller, Caitlyn</au><au>Beshiri, Michael L.</au><au>Agarwal, Supreet</au><au>Fang, Lei</au><au>Hynes, Paul G.</au><au>Alilin, Aian Neil</au><au>Lake, Ross</au><au>Abbey, Yasmine C.</au><au>Cawley, Jacob</au><au>Tice, Caitlin M.</au><au>Yin, JuanJuan</au><au>McKnight, Crystal</au><au>Klummp-Thomas, Carleen</au><au>Zhang, Xiaohu</au><au>Guha, Rajarshi</au><au>Hoover, Shelley</au><au>Simpson, R. Mark</au><au>Nguyen, Holly M.</au><au>Corey, Eva</au><au>Thomas, Craig J.</au><au>Proia, David A.</au><au>Kelly, Kathleen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-throughput screens identify HSP90 inhibitors as potent therapeutics that target inter-related growth and survival pathways in advanced prostate cancer</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2018-11-22</date><risdate>2018</risdate><volume>8</volume><issue>1</issue><spage>17239</spage><epage>13</epage><pages>17239-13</pages><artnum>17239</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The development of new treatments for castrate resistant prostate cancer (CRPC) must address such challenges as intrinsic tumor heterogeneity and phenotypic plasticity. Combined
PTEN/
TP53 alterations represent a major genotype of CRPC (25–30%) and are associated with poor outcomes. Using tumor-derived, castration-resistant
Pten/Tp53
null luminal prostate cells for comprehensive, high-throughput, mechanism-based screening, we identified several vulnerabilities among >1900 compounds, including inhibitors of: PI3K/AKT/mTOR, the proteasome, the cell cycle, heat shock proteins, DNA repair, NFκB, MAPK, and epigenetic modifiers. HSP90 inhibitors were one of the most active compound classes in the screen and have clinical potential for use in drug combinations to enhance efficacy and delay the development of resistance. To inform future design of rational drug combinations, we tested ganetespib, a potent second-generation HSP90 inhibitor, as a single agent in multiple CRPC genotypes and phenotypes. Ganetespib decreased growth of endogenous
Pten/Tp53
null tumors, confirming therapeutic activity
in situ
. Fifteen human CRPC LuCaP PDX-derived organoid models were assayed for responses to 110 drugs, and HSP90 inhibitors (ganetespib and onalespib) were among the select group of drugs (<10%) that demonstrated broad activity (>75% of models) at high potency (IC50 <1 µM). Ganetespib inhibits multiple targets, including AR and PI3K pathways, which regulate mutually compensatory growth and survival signals in some forms of CRPC. Combined with castration, ganetespib displayed deeper PDX tumor regressions and delayed castration resistance relative to either monotherapy. In all, comprehensive data from near-patient models presents novel contexts for HSP90 inhibition in multiple CRPC genotypes and phenotypes, expands upon HSP90 inhibitors as simultaneous inhibitors of oncogenic signaling and resistance mechanisms, and suggests utility for combined HSP90/AR inhibition in CRPC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30467317</pmid><doi>10.1038/s41598-018-35417-0</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Scientific reports, 2018-11, Vol.8 (1), p.17239-13, Article 17239 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6250716 |
| source | Nature Free; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 1-Phosphatidylinositol 3-kinase 13 13/106 631/67/589/466 631/67/70 64 AKT protein Castration Cell cycle DNA repair Drug development Epigenetics Genotypes Heat shock proteins Hsp90 protein Humanities and Social Sciences MAP kinase multidisciplinary NF-κB protein Organoids p53 Protein Phenotypes Phenotypic plasticity Prostate cancer Proteasomes PTEN protein Science Science (multidisciplinary) TOR protein Tumors |
| title | High-throughput screens identify HSP90 inhibitors as potent therapeutics that target inter-related growth and survival pathways in advanced prostate cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T03%3A58%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High-throughput%20screens%20identify%20HSP90%20inhibitors%20as%20potent%20therapeutics%20that%20target%20inter-related%20growth%20and%20survival%20pathways%20in%20advanced%20prostate%20cancer&rft.jtitle=Scientific%20reports&rft.au=Jansson,%20Keith%20H.&rft.date=2018-11-22&rft.volume=8&rft.issue=1&rft.spage=17239&rft.epage=13&rft.pages=17239-13&rft.artnum=17239&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-018-35417-0&rft_dat=%3Cproquest_pubme%3E2137461959%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2136901868&rft_id=info:pmid/30467317&rfr_iscdi=true |