HSP90 inhibition sensitizes head and neck cancer to platin-based chemoradiotherapy by modulation of the DNA damage response resulting in chromosomal fragmentation
Concurrent cisplatin radiotherapy (CCRT) is a current standard-of-care for locally advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT is frequently ineffective in patients with advanced disease. It has previously been shown that HSP90 inhibitors act as radiosensitizers, but these...
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| Veröffentlicht in: | BMC cancer 2017-01, Vol.17 (1), p.86, Article 86 |
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| creator | McLaughlin, Martin Barker, Holly E Khan, Aadil A Pedersen, Malin Dillon, Magnus Mansfield, David C Patel, Radhika Kyula, Joan N Bhide, Shreerang A Newbold, Kate L Nutting, Christopher M Harrington, Kevin J |
| description | Concurrent cisplatin radiotherapy (CCRT) is a current standard-of-care for locally advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT is frequently ineffective in patients with advanced disease. It has previously been shown that HSP90 inhibitors act as radiosensitizers, but these studies have not focused on CCRT in HNSCC. Here, we evaluated the HSP90 inhibitor, AUY922, combined with CCRT.
The ability of AUY922 to sensitize to CCRT was assessed in p53 mutant head and neck cell lines by clonogenic assay. Modulation of the CCRT induced DNA damage response (DDR) by AUY922 was characterized by confocal image analysis of RAD51, BRCA1, 53BP1, ATM and mutant p53 signaling. The role of FANCA depletion by AUY922 was examined using shRNA. Cell cycle checkpoint abrogation and chromosomal fragmentation was assessed by western blot, FACS and confocal. The role of ATM was also assessed by shRNA. AUY922 in combination with CCRT was assessed in vivo.
The combination of AUY922 with cisplatin, radiation and CCRT was found to be synergistic in p53 mutant HNSCC. AUY922 leads to significant alterations to the DDR induced by CCRT. This comprises inhibition of homologous recombination through decreased RAD51 and pS1524 BRCA1 with a corresponding increase in 53BP1 foci, activation of ATM and signaling into mutant p53. A shift to more error prone repair combined with a loss of checkpoint function leads to fragmentation of chromosomal material. The degree of disruption to DDR signalling correlated to chromosomal fragmentation and loss of clonogenicity. ATM shRNA indicated a possible rationale for the combination of AUY922 and CCRT in cells lacking ATM function.
This study supports future clinical studies combining AUY922 and CCRT in p53 mutant HNSCC. Modulation of the DDR and chromosomal fragmentation are likely to be analytical points of interest in such trials. |
| doi_str_mv | 10.1186/s12885-017-3084-0 |
| format | Article |
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The ability of AUY922 to sensitize to CCRT was assessed in p53 mutant head and neck cell lines by clonogenic assay. Modulation of the CCRT induced DNA damage response (DDR) by AUY922 was characterized by confocal image analysis of RAD51, BRCA1, 53BP1, ATM and mutant p53 signaling. The role of FANCA depletion by AUY922 was examined using shRNA. Cell cycle checkpoint abrogation and chromosomal fragmentation was assessed by western blot, FACS and confocal. The role of ATM was also assessed by shRNA. AUY922 in combination with CCRT was assessed in vivo.
The combination of AUY922 with cisplatin, radiation and CCRT was found to be synergistic in p53 mutant HNSCC. AUY922 leads to significant alterations to the DDR induced by CCRT. This comprises inhibition of homologous recombination through decreased RAD51 and pS1524 BRCA1 with a corresponding increase in 53BP1 foci, activation of ATM and signaling into mutant p53. A shift to more error prone repair combined with a loss of checkpoint function leads to fragmentation of chromosomal material. The degree of disruption to DDR signalling correlated to chromosomal fragmentation and loss of clonogenicity. ATM shRNA indicated a possible rationale for the combination of AUY922 and CCRT in cells lacking ATM function.
This study supports future clinical studies combining AUY922 and CCRT in p53 mutant HNSCC. Modulation of the DDR and chromosomal fragmentation are likely to be analytical points of interest in such trials.</description><identifier>ISSN: 1471-2407</identifier><identifier>EISSN: 1471-2407</identifier><identifier>DOI: 10.1186/s12885-017-3084-0</identifier><identifier>PMID: 28143445</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Animals ; Antibodies ; Antigens ; Automation ; BRCA1 Protein - genetics ; Carcinoma, Squamous Cell - drug therapy ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - radiotherapy ; Care and treatment ; Cell cycle ; Cell Line, Tumor ; Chemoradiotherapy - methods ; Chromosomes - drug effects ; Chromosomes - genetics ; Cisplatin ; DNA damage ; DNA Damage - drug effects ; DNA Damage - genetics ; DNA Damage - radiation effects ; DNA Fragmentation - drug effects ; DNA repair ; DNA Repair - drug effects ; DNA Repair - genetics ; DNA Repair - radiation effects ; Dosage and administration ; Female ; Head and neck cancer ; Head and Neck Neoplasms - drug therapy ; Head and Neck Neoplasms - genetics ; Head and Neck Neoplasms - metabolism ; Head and Neck Neoplasms - radiotherapy ; Homologous Recombination - drug effects ; HSP90 Heat-Shock Proteins - antagonists & inhibitors ; Human papillomavirus ; Humans ; Isoxazoles - pharmacology ; Medical prognosis ; Mice, Inbred BALB C ; Mice, Nude ; Organoplatinum Compounds - pharmacology ; Plasmids ; Protein Kinase Inhibitors - pharmacology ; Proteins ; Radiation therapy ; Radiotherapy ; Resorcinols - pharmacology ; Squamous Cell Carcinoma of Head and Neck ; Tumor Suppressor Protein p53 - genetics</subject><ispartof>BMC cancer, 2017-01, Vol.17 (1), p.86, Article 86</ispartof><rights>COPYRIGHT 2017 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2017</rights><rights>The Author(s). 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c559t-56d2ed0bf6d9cc27c249278e1f2eb9089a368bfbb4985277c212b943439861733</citedby><cites>FETCH-LOGICAL-c559t-56d2ed0bf6d9cc27c249278e1f2eb9089a368bfbb4985277c212b943439861733</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/PMC5282703/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282703/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28143445$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McLaughlin, Martin</creatorcontrib><creatorcontrib>Barker, Holly E</creatorcontrib><creatorcontrib>Khan, Aadil A</creatorcontrib><creatorcontrib>Pedersen, Malin</creatorcontrib><creatorcontrib>Dillon, Magnus</creatorcontrib><creatorcontrib>Mansfield, David C</creatorcontrib><creatorcontrib>Patel, Radhika</creatorcontrib><creatorcontrib>Kyula, Joan N</creatorcontrib><creatorcontrib>Bhide, Shreerang A</creatorcontrib><creatorcontrib>Newbold, Kate L</creatorcontrib><creatorcontrib>Nutting, Christopher M</creatorcontrib><creatorcontrib>Harrington, Kevin J</creatorcontrib><title>HSP90 inhibition sensitizes head and neck cancer to platin-based chemoradiotherapy by modulation of the DNA damage response resulting in chromosomal fragmentation</title><title>BMC cancer</title><addtitle>BMC Cancer</addtitle><description>Concurrent cisplatin radiotherapy (CCRT) is a current standard-of-care for locally advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT is frequently ineffective in patients with advanced disease. It has previously been shown that HSP90 inhibitors act as radiosensitizers, but these studies have not focused on CCRT in HNSCC. Here, we evaluated the HSP90 inhibitor, AUY922, combined with CCRT.
The ability of AUY922 to sensitize to CCRT was assessed in p53 mutant head and neck cell lines by clonogenic assay. Modulation of the CCRT induced DNA damage response (DDR) by AUY922 was characterized by confocal image analysis of RAD51, BRCA1, 53BP1, ATM and mutant p53 signaling. The role of FANCA depletion by AUY922 was examined using shRNA. Cell cycle checkpoint abrogation and chromosomal fragmentation was assessed by western blot, FACS and confocal. The role of ATM was also assessed by shRNA. AUY922 in combination with CCRT was assessed in vivo.
The combination of AUY922 with cisplatin, radiation and CCRT was found to be synergistic in p53 mutant HNSCC. AUY922 leads to significant alterations to the DDR induced by CCRT. This comprises inhibition of homologous recombination through decreased RAD51 and pS1524 BRCA1 with a corresponding increase in 53BP1 foci, activation of ATM and signaling into mutant p53. A shift to more error prone repair combined with a loss of checkpoint function leads to fragmentation of chromosomal material. The degree of disruption to DDR signalling correlated to chromosomal fragmentation and loss of clonogenicity. ATM shRNA indicated a possible rationale for the combination of AUY922 and CCRT in cells lacking ATM function.
This study supports future clinical studies combining AUY922 and CCRT in p53 mutant HNSCC. Modulation of the DDR and chromosomal fragmentation are likely to be analytical points of interest in such trials.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Automation</subject><subject>BRCA1 Protein - genetics</subject><subject>Carcinoma, Squamous Cell - drug therapy</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - radiotherapy</subject><subject>Care and treatment</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Chemoradiotherapy - methods</subject><subject>Chromosomes - drug effects</subject><subject>Chromosomes - genetics</subject><subject>Cisplatin</subject><subject>DNA damage</subject><subject>DNA Damage - drug effects</subject><subject>DNA Damage - genetics</subject><subject>DNA Damage - radiation effects</subject><subject>DNA Fragmentation - drug effects</subject><subject>DNA repair</subject><subject>DNA Repair - drug effects</subject><subject>DNA Repair - genetics</subject><subject>DNA Repair - radiation effects</subject><subject>Dosage and administration</subject><subject>Female</subject><subject>Head and neck cancer</subject><subject>Head and Neck Neoplasms - drug therapy</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Head and Neck Neoplasms - metabolism</subject><subject>Head and Neck Neoplasms - radiotherapy</subject><subject>Homologous Recombination - drug effects</subject><subject>HSP90 Heat-Shock Proteins - antagonists & inhibitors</subject><subject>Human papillomavirus</subject><subject>Humans</subject><subject>Isoxazoles - pharmacology</subject><subject>Medical prognosis</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Organoplatinum Compounds - pharmacology</subject><subject>Plasmids</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Proteins</subject><subject>Radiation therapy</subject><subject>Radiotherapy</subject><subject>Resorcinols - pharmacology</subject><subject>Squamous Cell Carcinoma of Head and Neck</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><issn>1471-2407</issn><issn>1471-2407</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkt-K1TAQxoso7rr6AN5IQBC86JqkaZvcCIf1zy4sKq5ehzSZtlnbpCateHwcn9R0z7qeA5KLDJnffBNmvix7SvApIbx6FQnlvMwxqfMCc5bje9kxYTXJKcP1_b34KHsU4zVOIMf8YXZEOWEFY-Vx9vv86pPAyLreNna23qEILqboF0TUgzJIOYMc6G9IK6choNmjaVCzdXmjIhikexh9UMb6uYegpi1qtmj0ZlmhpOdblBLozYcNMmpUHaAAcfIu3gTLkJS61D_pBD_66Ec1oDaobgQ33yg8zh60aojw5PY-yb6-e_vl7Dy__Pj-4mxzmeuyFHNeVoaCwU1bGaE1rTVlgtYcSEuhEZgLVVS8aZuGCV7SOuUJbUQaQyF4ReqiOMle73SnpRnB6NQ_qEFOwY4qbKVXVh5mnO1l53_IknJa41Xg-a1A8N8XiLO89ktw6c8ybavgnNVF-Y_q1ADSutYnMT3aqOWGcVyyWuAqUaf_odIxMFrtHbQ2vR8UvDwoSMwMP-dOLTHKi6vPh-yLPTZteZj76IdlnXY8BMkO1MHHGKC9mwbBcrWg3FlQJmfJ1YISp5pn-2O8q_jrueIPZu3Xfg</recordid><startdate>20170131</startdate><enddate>20170131</enddate><creator>McLaughlin, Martin</creator><creator>Barker, Holly E</creator><creator>Khan, Aadil A</creator><creator>Pedersen, Malin</creator><creator>Dillon, Magnus</creator><creator>Mansfield, David C</creator><creator>Patel, Radhika</creator><creator>Kyula, Joan N</creator><creator>Bhide, Shreerang A</creator><creator>Newbold, Kate L</creator><creator>Nutting, Christopher M</creator><creator>Harrington, Kevin J</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>ISR</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20170131</creationdate><title>HSP90 inhibition sensitizes head and neck cancer to platin-based chemoradiotherapy by modulation of the DNA damage response resulting in chromosomal fragmentation</title><author>McLaughlin, Martin ; Barker, Holly E ; Khan, Aadil A ; Pedersen, Malin ; Dillon, Magnus ; Mansfield, David C ; Patel, Radhika ; Kyula, Joan N ; Bhide, Shreerang A ; Newbold, Kate L ; Nutting, Christopher M ; Harrington, Kevin J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c559t-56d2ed0bf6d9cc27c249278e1f2eb9089a368bfbb4985277c212b943439861733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Automation</topic><topic>BRCA1 Protein - genetics</topic><topic>Carcinoma, Squamous Cell - drug therapy</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - radiotherapy</topic><topic>Care and treatment</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Chemoradiotherapy - methods</topic><topic>Chromosomes - drug effects</topic><topic>Chromosomes - genetics</topic><topic>Cisplatin</topic><topic>DNA damage</topic><topic>DNA Damage - drug effects</topic><topic>DNA Damage - genetics</topic><topic>DNA Damage - radiation effects</topic><topic>DNA Fragmentation - drug effects</topic><topic>DNA repair</topic><topic>DNA Repair - drug effects</topic><topic>DNA Repair - genetics</topic><topic>DNA Repair - radiation effects</topic><topic>Dosage and administration</topic><topic>Female</topic><topic>Head and neck cancer</topic><topic>Head and Neck Neoplasms - drug therapy</topic><topic>Head and Neck Neoplasms - genetics</topic><topic>Head and Neck Neoplasms - metabolism</topic><topic>Head and Neck Neoplasms - radiotherapy</topic><topic>Homologous Recombination - drug effects</topic><topic>HSP90 Heat-Shock Proteins - antagonists & inhibitors</topic><topic>Human papillomavirus</topic><topic>Humans</topic><topic>Isoxazoles - pharmacology</topic><topic>Medical prognosis</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Organoplatinum Compounds - pharmacology</topic><topic>Plasmids</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Proteins</topic><topic>Radiation therapy</topic><topic>Radiotherapy</topic><topic>Resorcinols - pharmacology</topic><topic>Squamous Cell Carcinoma of Head and Neck</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McLaughlin, Martin</creatorcontrib><creatorcontrib>Barker, Holly E</creatorcontrib><creatorcontrib>Khan, Aadil A</creatorcontrib><creatorcontrib>Pedersen, Malin</creatorcontrib><creatorcontrib>Dillon, Magnus</creatorcontrib><creatorcontrib>Mansfield, David C</creatorcontrib><creatorcontrib>Patel, Radhika</creatorcontrib><creatorcontrib>Kyula, Joan N</creatorcontrib><creatorcontrib>Bhide, Shreerang A</creatorcontrib><creatorcontrib>Newbold, Kate L</creatorcontrib><creatorcontrib>Nutting, Christopher M</creatorcontrib><creatorcontrib>Harrington, Kevin J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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 Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</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>PubMed Central (Full Participant titles)</collection><jtitle>BMC cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McLaughlin, Martin</au><au>Barker, Holly E</au><au>Khan, Aadil A</au><au>Pedersen, Malin</au><au>Dillon, Magnus</au><au>Mansfield, David C</au><au>Patel, Radhika</au><au>Kyula, Joan N</au><au>Bhide, Shreerang A</au><au>Newbold, Kate L</au><au>Nutting, Christopher M</au><au>Harrington, Kevin J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HSP90 inhibition sensitizes head and neck cancer to platin-based chemoradiotherapy by modulation of the DNA damage response resulting in chromosomal fragmentation</atitle><jtitle>BMC cancer</jtitle><addtitle>BMC Cancer</addtitle><date>2017-01-31</date><risdate>2017</risdate><volume>17</volume><issue>1</issue><spage>86</spage><pages>86-</pages><artnum>86</artnum><issn>1471-2407</issn><eissn>1471-2407</eissn><abstract>Concurrent cisplatin radiotherapy (CCRT) is a current standard-of-care for locally advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT is frequently ineffective in patients with advanced disease. It has previously been shown that HSP90 inhibitors act as radiosensitizers, but these studies have not focused on CCRT in HNSCC. Here, we evaluated the HSP90 inhibitor, AUY922, combined with CCRT.
The ability of AUY922 to sensitize to CCRT was assessed in p53 mutant head and neck cell lines by clonogenic assay. Modulation of the CCRT induced DNA damage response (DDR) by AUY922 was characterized by confocal image analysis of RAD51, BRCA1, 53BP1, ATM and mutant p53 signaling. The role of FANCA depletion by AUY922 was examined using shRNA. Cell cycle checkpoint abrogation and chromosomal fragmentation was assessed by western blot, FACS and confocal. The role of ATM was also assessed by shRNA. AUY922 in combination with CCRT was assessed in vivo.
The combination of AUY922 with cisplatin, radiation and CCRT was found to be synergistic in p53 mutant HNSCC. AUY922 leads to significant alterations to the DDR induced by CCRT. This comprises inhibition of homologous recombination through decreased RAD51 and pS1524 BRCA1 with a corresponding increase in 53BP1 foci, activation of ATM and signaling into mutant p53. A shift to more error prone repair combined with a loss of checkpoint function leads to fragmentation of chromosomal material. The degree of disruption to DDR signalling correlated to chromosomal fragmentation and loss of clonogenicity. ATM shRNA indicated a possible rationale for the combination of AUY922 and CCRT in cells lacking ATM function.
This study supports future clinical studies combining AUY922 and CCRT in p53 mutant HNSCC. Modulation of the DDR and chromosomal fragmentation are likely to be analytical points of interest in such trials.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>28143445</pmid><doi>10.1186/s12885-017-3084-0</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | BMC cancer, 2017-01, Vol.17 (1), p.86, Article 86 |
| issn | 1471-2407 1471-2407 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; SpringerLink Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access; Springer Nature OA Free Journals |
| subjects | Animals Antibodies Antigens Automation BRCA1 Protein - genetics Carcinoma, Squamous Cell - drug therapy Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - radiotherapy Care and treatment Cell cycle Cell Line, Tumor Chemoradiotherapy - methods Chromosomes - drug effects Chromosomes - genetics Cisplatin DNA damage DNA Damage - drug effects DNA Damage - genetics DNA Damage - radiation effects DNA Fragmentation - drug effects DNA repair DNA Repair - drug effects DNA Repair - genetics DNA Repair - radiation effects Dosage and administration Female Head and neck cancer Head and Neck Neoplasms - drug therapy Head and Neck Neoplasms - genetics Head and Neck Neoplasms - metabolism Head and Neck Neoplasms - radiotherapy Homologous Recombination - drug effects HSP90 Heat-Shock Proteins - antagonists & inhibitors Human papillomavirus Humans Isoxazoles - pharmacology Medical prognosis Mice, Inbred BALB C Mice, Nude Organoplatinum Compounds - pharmacology Plasmids Protein Kinase Inhibitors - pharmacology Proteins Radiation therapy Radiotherapy Resorcinols - pharmacology Squamous Cell Carcinoma of Head and Neck Tumor Suppressor Protein p53 - genetics |
| title | HSP90 inhibition sensitizes head and neck cancer to platin-based chemoradiotherapy by modulation of the DNA damage response resulting in chromosomal fragmentation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T05%3A34%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=HSP90%20inhibition%20sensitizes%20head%20and%20neck%20cancer%20to%20platin-based%20chemoradiotherapy%20by%20modulation%20of%20the%20DNA%20damage%20response%20resulting%20in%20chromosomal%20fragmentation&rft.jtitle=BMC%20cancer&rft.au=McLaughlin,%20Martin&rft.date=2017-01-31&rft.volume=17&rft.issue=1&rft.spage=86&rft.pages=86-&rft.artnum=86&rft.issn=1471-2407&rft.eissn=1471-2407&rft_id=info:doi/10.1186/s12885-017-3084-0&rft_dat=%3Cgale_pubme%3EA480547906%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1863884735&rft_id=info:pmid/28143445&rft_galeid=A480547906&rfr_iscdi=true |