Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas
HSP90, a highly conserved molecular chaperone that regulates the function of several oncogenic client proteins, is altered in glioblastoma. However, HSP90 inhibitors currently in clinical trials are short-acting, have unacceptable toxicities, or are unable to cross the blood-brain barrier (BBB). We...
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| Veröffentlicht in: | Clinical cancer research 2017-10, Vol.23 (20), p.6215-6226 |
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| creator | Canella, Alessandro Welker, Alessandra M Yoo, Ji Young Xu, Jihong Abas, Fazly S Kesanakurti, Divya Nagarajan, Prabakaran Beattie, Christine E Sulman, Erik P Liu, Joseph Gumin, Joy Lang, Frederick F Gurcan, Metin N Kaur, Balveen Sampath, Deepa Puduvalli, Vinay K |
| description | HSP90, a highly conserved molecular chaperone that regulates the function of several oncogenic client proteins, is altered in glioblastoma. However, HSP90 inhibitors currently in clinical trials are short-acting, have unacceptable toxicities, or are unable to cross the blood-brain barrier (BBB). We examined the efficacy of onalespib, a potent, long-acting novel HSP90 inhibitor as a single agent and in combination with temozolomide (TMZ) against gliomas
and
The effect of onalespib on HSP90, its client proteins, and on the biology of glioma cell lines and patient-derived glioma-initiating cells (GSC) was determined. Brain and plasma pharmacokinetics of onalespib and its ability to inhibit HSP90
were assessed in non-tumor-bearing mice. Its efficacy as a single agent or in combination with TMZ was assessed
and
using zebrafish and patient-derived GSC xenograft mouse glioma models.
Onalespib-mediated HSP90 inhibition depleted several survival-promoting client proteins such as EGFR, EGFRvIII, and AKT, disrupted their downstream signaling, and decreased the proliferation, migration, angiogenesis, and survival of glioma cell lines and GSCs. Onalespib effectively crossed the BBB to inhibit HSP90
and extended survival as a single agent in zebrafish xenografts and in combination with TMZ in both zebrafish and GSC mouse xenografts.
Our results demonstrate the long-acting effects of onalespib against gliomas
and
which combined with its ability to cross the BBB support its development as a potential therapeutic agent in combination with TMZ against gliomas.
. |
| doi_str_mv | 10.1158/1078-0432.CCR-16-3151 |
| format | Article |
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and
The effect of onalespib on HSP90, its client proteins, and on the biology of glioma cell lines and patient-derived glioma-initiating cells (GSC) was determined. Brain and plasma pharmacokinetics of onalespib and its ability to inhibit HSP90
were assessed in non-tumor-bearing mice. Its efficacy as a single agent or in combination with TMZ was assessed
and
using zebrafish and patient-derived GSC xenograft mouse glioma models.
Onalespib-mediated HSP90 inhibition depleted several survival-promoting client proteins such as EGFR, EGFRvIII, and AKT, disrupted their downstream signaling, and decreased the proliferation, migration, angiogenesis, and survival of glioma cell lines and GSCs. Onalespib effectively crossed the BBB to inhibit HSP90
and extended survival as a single agent in zebrafish xenografts and in combination with TMZ in both zebrafish and GSC mouse xenografts.
Our results demonstrate the long-acting effects of onalespib against gliomas
and
which combined with its ability to cross the BBB support its development as a potential therapeutic agent in combination with TMZ against gliomas.
.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-16-3151</identifier><identifier>PMID: 28679777</identifier><language>eng</language><publisher>United States: American Association for Cancer Research Inc</publisher><subject>AKT protein ; Angiogenesis ; Animal models ; Animals ; Antineoplastic Agents - pharmacokinetics ; Antineoplastic Agents - pharmacology ; Benzamides - pharmacokinetics ; Benzamides - pharmacology ; Biological effects ; Biotechnology ; Blood-brain barrier ; Blood-Brain Barrier - metabolism ; Brain ; Brain tumors ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Cell survival ; Chemical compounds ; Clinical trials ; Dacarbazine - analogs & derivatives ; Dacarbazine - pharmacokinetics ; Dacarbazine - pharmacology ; Danio rerio ; Disease Models, Animal ; Drug Synergism ; Drug Therapy, Combination ; Effectiveness ; Epidermal growth factor receptors ; ErbB Receptors - metabolism ; Experimental design ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Female ; Gene Expression ; Glioblastoma ; Glioma - drug therapy ; Glioma - metabolism ; Glioma - mortality ; Glioma - pathology ; Glioma cells ; HSP90 Heat-Shock Proteins - antagonists & inhibitors ; HSP90 Heat-Shock Proteins - genetics ; HSP90 Heat-Shock Proteins - metabolism ; Hsp90 protein ; Humans ; Inhibitors ; Isoindoles - pharmacokinetics ; Isoindoles - pharmacology ; Medical research ; Mice ; Neoplastic Stem Cells - metabolism ; Pharmacokinetics ; Pharmacology ; Protein Transport ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Ribosomal Protein S6 Kinases - metabolism ; Signal Transduction - drug effects ; Signaling ; Survival ; Survival Rate ; Temozolomide ; Toxicity ; Xenograft Model Antitumor Assays ; Xenografts ; Zebrafish</subject><ispartof>Clinical cancer research, 2017-10, Vol.23 (20), p.6215-6226</ispartof><rights>2017 American Association for Cancer Research.</rights><rights>Copyright American Association for Cancer Research Inc Oct 15, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-a621b13e22c319e528c04d0c1cf5f331ea95f8e94472ce2c7f48330fdb3910173</citedby><cites>FETCH-LOGICAL-c439t-a621b13e22c319e528c04d0c1cf5f331ea95f8e94472ce2c7f48330fdb3910173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28679777$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Canella, Alessandro</creatorcontrib><creatorcontrib>Welker, Alessandra M</creatorcontrib><creatorcontrib>Yoo, Ji Young</creatorcontrib><creatorcontrib>Xu, Jihong</creatorcontrib><creatorcontrib>Abas, Fazly S</creatorcontrib><creatorcontrib>Kesanakurti, Divya</creatorcontrib><creatorcontrib>Nagarajan, Prabakaran</creatorcontrib><creatorcontrib>Beattie, Christine E</creatorcontrib><creatorcontrib>Sulman, Erik P</creatorcontrib><creatorcontrib>Liu, Joseph</creatorcontrib><creatorcontrib>Gumin, Joy</creatorcontrib><creatorcontrib>Lang, Frederick F</creatorcontrib><creatorcontrib>Gurcan, Metin N</creatorcontrib><creatorcontrib>Kaur, Balveen</creatorcontrib><creatorcontrib>Sampath, Deepa</creatorcontrib><creatorcontrib>Puduvalli, Vinay K</creatorcontrib><title>Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>HSP90, a highly conserved molecular chaperone that regulates the function of several oncogenic client proteins, is altered in glioblastoma. However, HSP90 inhibitors currently in clinical trials are short-acting, have unacceptable toxicities, or are unable to cross the blood-brain barrier (BBB). We examined the efficacy of onalespib, a potent, long-acting novel HSP90 inhibitor as a single agent and in combination with temozolomide (TMZ) against gliomas
and
The effect of onalespib on HSP90, its client proteins, and on the biology of glioma cell lines and patient-derived glioma-initiating cells (GSC) was determined. Brain and plasma pharmacokinetics of onalespib and its ability to inhibit HSP90
were assessed in non-tumor-bearing mice. Its efficacy as a single agent or in combination with TMZ was assessed
and
using zebrafish and patient-derived GSC xenograft mouse glioma models.
Onalespib-mediated HSP90 inhibition depleted several survival-promoting client proteins such as EGFR, EGFRvIII, and AKT, disrupted their downstream signaling, and decreased the proliferation, migration, angiogenesis, and survival of glioma cell lines and GSCs. Onalespib effectively crossed the BBB to inhibit HSP90
and extended survival as a single agent in zebrafish xenografts and in combination with TMZ in both zebrafish and GSC mouse xenografts.
Our results demonstrate the long-acting effects of onalespib against gliomas
and
which combined with its ability to cross the BBB support its development as a potential therapeutic agent in combination with TMZ against gliomas.
.</description><subject>AKT protein</subject><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Benzamides - pharmacokinetics</subject><subject>Benzamides - pharmacology</subject><subject>Biological effects</subject><subject>Biotechnology</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Brain</subject><subject>Brain tumors</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell survival</subject><subject>Chemical compounds</subject><subject>Clinical trials</subject><subject>Dacarbazine - analogs & derivatives</subject><subject>Dacarbazine - pharmacokinetics</subject><subject>Dacarbazine - pharmacology</subject><subject>Danio rerio</subject><subject>Disease Models, Animal</subject><subject>Drug Synergism</subject><subject>Drug Therapy, Combination</subject><subject>Effectiveness</subject><subject>Epidermal growth factor receptors</subject><subject>ErbB Receptors - metabolism</subject><subject>Experimental design</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Glioblastoma</subject><subject>Glioma - drug therapy</subject><subject>Glioma - metabolism</subject><subject>Glioma - mortality</subject><subject>Glioma - pathology</subject><subject>Glioma cells</subject><subject>HSP90 Heat-Shock Proteins - antagonists & inhibitors</subject><subject>HSP90 Heat-Shock Proteins - genetics</subject><subject>HSP90 Heat-Shock Proteins - metabolism</subject><subject>Hsp90 protein</subject><subject>Humans</subject><subject>Inhibitors</subject><subject>Isoindoles - pharmacokinetics</subject><subject>Isoindoles - pharmacology</subject><subject>Medical research</subject><subject>Mice</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>Protein Transport</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Ribosomal Protein S6 Kinases - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Signaling</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Temozolomide</subject><subject>Toxicity</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><subject>Zebrafish</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkdFqHCEUhofS0qRpH6FF6G0n9eg4jjeFZUg2gS0J3fRaHEdnDTO61dmG5EnyuHXZJDRXCv7f7-F8RfEZ8CkAa74D5k2JK0pO2_ZXCXVJgcGb4hgY4yUlNXub78-Zo-JDSrcYQwW4el8ckabmgnN-XDyeWeu00vcoWHTl1WjS1nXfkEKr4IdyoWfnB7Q2Ovi-XBpvoppd8OhifS0wuvQb17k5xAykzKxzeDRoMRg_I-V75Dxqw9Q5f6Du3LxBN2YKD2EMk-sNUoNyPs3opxrd4FXGlqMLk0ofi3dWjcl8ejpPit_nZzftRbm6Wl62i1WpKyrmUtUEOqCGEE1BGEYajasea9CWWUrBKMFsY0RVcaIN0dxWDaXY9h0VgIHTk-LHoXe76ybT6zx5VKPcRjepeC-DcvL1i3cbOYS_kommzvvNBV-fCmL4szNplrdhF_MmkwTR0ApqSlhOsUNKx5BSNPblB8ByL1TuZcm9LJmFSqjlXmjmvvw_3gv1bJD-AzCfnZU</recordid><startdate>20171015</startdate><enddate>20171015</enddate><creator>Canella, Alessandro</creator><creator>Welker, Alessandra M</creator><creator>Yoo, Ji Young</creator><creator>Xu, Jihong</creator><creator>Abas, Fazly S</creator><creator>Kesanakurti, Divya</creator><creator>Nagarajan, Prabakaran</creator><creator>Beattie, Christine E</creator><creator>Sulman, Erik P</creator><creator>Liu, Joseph</creator><creator>Gumin, Joy</creator><creator>Lang, Frederick F</creator><creator>Gurcan, Metin N</creator><creator>Kaur, Balveen</creator><creator>Sampath, Deepa</creator><creator>Puduvalli, Vinay K</creator><general>American Association for Cancer Research Inc</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>7QO</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20171015</creationdate><title>Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas</title><author>Canella, Alessandro ; Welker, Alessandra M ; Yoo, Ji Young ; Xu, Jihong ; Abas, Fazly S ; Kesanakurti, Divya ; Nagarajan, Prabakaran ; Beattie, Christine E ; Sulman, Erik P ; Liu, Joseph ; Gumin, Joy ; Lang, Frederick F ; Gurcan, Metin N ; Kaur, Balveen ; Sampath, Deepa ; Puduvalli, Vinay K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-a621b13e22c319e528c04d0c1cf5f331ea95f8e94472ce2c7f48330fdb3910173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>AKT protein</topic><topic>Angiogenesis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Benzamides - pharmacokinetics</topic><topic>Benzamides - pharmacology</topic><topic>Biological effects</topic><topic>Biotechnology</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Brain</topic><topic>Brain tumors</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell survival</topic><topic>Chemical compounds</topic><topic>Clinical trials</topic><topic>Dacarbazine - analogs & derivatives</topic><topic>Dacarbazine - pharmacokinetics</topic><topic>Dacarbazine - pharmacology</topic><topic>Danio rerio</topic><topic>Disease Models, Animal</topic><topic>Drug Synergism</topic><topic>Drug Therapy, Combination</topic><topic>Effectiveness</topic><topic>Epidermal growth factor receptors</topic><topic>ErbB Receptors - metabolism</topic><topic>Experimental design</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Glioblastoma</topic><topic>Glioma - drug therapy</topic><topic>Glioma - metabolism</topic><topic>Glioma - mortality</topic><topic>Glioma - pathology</topic><topic>Glioma cells</topic><topic>HSP90 Heat-Shock Proteins - antagonists & inhibitors</topic><topic>HSP90 Heat-Shock Proteins - genetics</topic><topic>HSP90 Heat-Shock Proteins - metabolism</topic><topic>Hsp90 protein</topic><topic>Humans</topic><topic>Inhibitors</topic><topic>Isoindoles - pharmacokinetics</topic><topic>Isoindoles - pharmacology</topic><topic>Medical research</topic><topic>Mice</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Pharmacokinetics</topic><topic>Pharmacology</topic><topic>Protein Transport</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Ribosomal Protein S6 Kinases - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Signaling</topic><topic>Survival</topic><topic>Survival Rate</topic><topic>Temozolomide</topic><topic>Toxicity</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Canella, Alessandro</creatorcontrib><creatorcontrib>Welker, Alessandra M</creatorcontrib><creatorcontrib>Yoo, Ji Young</creatorcontrib><creatorcontrib>Xu, Jihong</creatorcontrib><creatorcontrib>Abas, Fazly S</creatorcontrib><creatorcontrib>Kesanakurti, Divya</creatorcontrib><creatorcontrib>Nagarajan, Prabakaran</creatorcontrib><creatorcontrib>Beattie, Christine E</creatorcontrib><creatorcontrib>Sulman, Erik P</creatorcontrib><creatorcontrib>Liu, Joseph</creatorcontrib><creatorcontrib>Gumin, Joy</creatorcontrib><creatorcontrib>Lang, Frederick F</creatorcontrib><creatorcontrib>Gurcan, Metin N</creatorcontrib><creatorcontrib>Kaur, Balveen</creatorcontrib><creatorcontrib>Sampath, Deepa</creatorcontrib><creatorcontrib>Puduvalli, Vinay K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Canella, Alessandro</au><au>Welker, Alessandra M</au><au>Yoo, Ji Young</au><au>Xu, Jihong</au><au>Abas, Fazly S</au><au>Kesanakurti, Divya</au><au>Nagarajan, Prabakaran</au><au>Beattie, Christine E</au><au>Sulman, Erik P</au><au>Liu, Joseph</au><au>Gumin, Joy</au><au>Lang, Frederick F</au><au>Gurcan, Metin N</au><au>Kaur, Balveen</au><au>Sampath, Deepa</au><au>Puduvalli, Vinay K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2017-10-15</date><risdate>2017</risdate><volume>23</volume><issue>20</issue><spage>6215</spage><epage>6226</epage><pages>6215-6226</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>HSP90, a highly conserved molecular chaperone that regulates the function of several oncogenic client proteins, is altered in glioblastoma. However, HSP90 inhibitors currently in clinical trials are short-acting, have unacceptable toxicities, or are unable to cross the blood-brain barrier (BBB). We examined the efficacy of onalespib, a potent, long-acting novel HSP90 inhibitor as a single agent and in combination with temozolomide (TMZ) against gliomas
and
The effect of onalespib on HSP90, its client proteins, and on the biology of glioma cell lines and patient-derived glioma-initiating cells (GSC) was determined. Brain and plasma pharmacokinetics of onalespib and its ability to inhibit HSP90
were assessed in non-tumor-bearing mice. Its efficacy as a single agent or in combination with TMZ was assessed
and
using zebrafish and patient-derived GSC xenograft mouse glioma models.
Onalespib-mediated HSP90 inhibition depleted several survival-promoting client proteins such as EGFR, EGFRvIII, and AKT, disrupted their downstream signaling, and decreased the proliferation, migration, angiogenesis, and survival of glioma cell lines and GSCs. Onalespib effectively crossed the BBB to inhibit HSP90
and extended survival as a single agent in zebrafish xenografts and in combination with TMZ in both zebrafish and GSC mouse xenografts.
Our results demonstrate the long-acting effects of onalespib against gliomas
and
which combined with its ability to cross the BBB support its development as a potential therapeutic agent in combination with TMZ against gliomas.
.</abstract><cop>United States</cop><pub>American Association for Cancer Research Inc</pub><pmid>28679777</pmid><doi>10.1158/1078-0432.CCR-16-3151</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2017-10, Vol.23 (20), p.6215-6226 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5986078 |
| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | AKT protein Angiogenesis Animal models Animals Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - pharmacology Benzamides - pharmacokinetics Benzamides - pharmacology Biological effects Biotechnology Blood-brain barrier Blood-Brain Barrier - metabolism Brain Brain tumors Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Cell survival Chemical compounds Clinical trials Dacarbazine - analogs & derivatives Dacarbazine - pharmacokinetics Dacarbazine - pharmacology Danio rerio Disease Models, Animal Drug Synergism Drug Therapy, Combination Effectiveness Epidermal growth factor receptors ErbB Receptors - metabolism Experimental design Extracellular Signal-Regulated MAP Kinases - metabolism Female Gene Expression Glioblastoma Glioma - drug therapy Glioma - metabolism Glioma - mortality Glioma - pathology Glioma cells HSP90 Heat-Shock Proteins - antagonists & inhibitors HSP90 Heat-Shock Proteins - genetics HSP90 Heat-Shock Proteins - metabolism Hsp90 protein Humans Inhibitors Isoindoles - pharmacokinetics Isoindoles - pharmacology Medical research Mice Neoplastic Stem Cells - metabolism Pharmacokinetics Pharmacology Protein Transport Proteins Proto-Oncogene Proteins c-akt - metabolism Ribosomal Protein S6 Kinases - metabolism Signal Transduction - drug effects Signaling Survival Survival Rate Temozolomide Toxicity Xenograft Model Antitumor Assays Xenografts Zebrafish |
| title | Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T05%3A44%3A48IST&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=Efficacy%20of%20Onalespib,%20a%20Long-Acting%20Second-Generation%20HSP90%20Inhibitor,%20as%20a%20Single%20Agent%20and%20in%20Combination%20with%20Temozolomide%20against%20Malignant%20Gliomas&rft.jtitle=Clinical%20cancer%20research&rft.au=Canella,%20Alessandro&rft.date=2017-10-15&rft.volume=23&rft.issue=20&rft.spage=6215&rft.epage=6226&rft.pages=6215-6226&rft.issn=1078-0432&rft.eissn=1557-3265&rft_id=info:doi/10.1158/1078-0432.CCR-16-3151&rft_dat=%3Cproquest_pubme%3E1983416325%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=1983416325&rft_id=info:pmid/28679777&rfr_iscdi=true |