Targeting HSF1 as a Therapeutic Strategy for Multiple Mechanisms of EGFR Inhibitor Resistance in EGFR Mutant Non-Small-Cell Lung Cancer
Although EGFR-TKI treatment of NSCLC (non-small-cell lung cancer) patients often achieves profound initial responses, the efficacy is transient due to acquired resistance. Multiple receptor tyrosine kinase (RTK) pathways contribute to the resistance of NSCLC to first- and third-generation EGFR-TKIs,...
Gespeichert in:
| Veröffentlicht in: | Cancers 2021-06, Vol.13 (12), p.2987 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 12 |
| container_start_page | 2987 |
| container_title | Cancers |
| container_volume | 13 |
| creator | Lee, Sangah Jung, Jiyae Lee, Yu-Jin Kim, Seon-Kyu Kim, Jung-Ae Kim, Bo-Kyung Park, Kyung Chan Kwon, Byoung-Mog Han, Dong Cho |
| description | Although EGFR-TKI treatment of NSCLC (non-small-cell lung cancer) patients often achieves profound initial responses, the efficacy is transient due to acquired resistance. Multiple receptor tyrosine kinase (RTK) pathways contribute to the resistance of NSCLC to first- and third-generation EGFR-TKIs, such as erlotinib and osimertinib. To identify potential targets for overcoming EGFR-TKI resistance, we performed a gene expression signature-based strategy using connectivity map (CMap) analysis. We generated erlotinib-resistant HCC827-ErlR cells, which showed resistance to erlotinib, gefitinib, osimertinib, and doxorubicin. A list of differentially expressed genes (DEGs) in HCC827-ErlR cells was generated and queried using CMap analysis. Analysis of the top 4 compounds from the CMap list suggested HSF1 as a potential target to overcome EGFR-TKI resistance. HSF1 inhibition by using HSF1 shRNAs or KRIBB11 decreased the expression of HSF1 downstream proteins, such as HSP70 and HSP27, and also decreased the expression of HSP90/HSP70/BAG3 client proteins, such as BCL2, MCL1, EGFR, MET, and AXL, causing apoptosis of EGFR-TKI-resistant cancer cells. Finally, we demonstrated the efficacy of the HSF1 inhibitor on PC9-ErlR cells expressing mutant EGFR (T790M) in vivo. Collectively, these findings support a targetable HSF1-(HSP90/HSP70/BAG3)-(BCL2/MCL1/EGFR/MET/AXL) pathway to overcome multiple mechanisms of EGFR-TKI resistance. |
| doi_str_mv | 10.3390/cancers13122987 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8232331</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2544958395</sourcerecordid><originalsourceid>FETCH-LOGICAL-c398t-7594030a50e0bb3328837f9f0b6b16b46ae3a9031f8e6a75929c08d171e6354d3</originalsourceid><addsrcrecordid>eNpdkUFrGzEQhUVoSUKac66CXHrZRtLsrlaXQjFxErBbiN3zopVnbYVdyZW0gfyC_u3KcSht5qIR8_H0noaQK86-ACh2Y7QzGCIHLoRq5Ak5F0yKoq5V-eGf_oxcxvjEcgFwWctTcgalYCCZOie_1zpsMVm3pferOac6Uk3XOwx6j1Oyhq5S0Am3L7T3gS6nIdn9gHSJZqedjWOkvqe3d_NH-uB2trMpU48YbUwHc9S643A55Xui370rVqMehmKGw0AXU3529priE_nY6yHi5dt5QX7Ob9ez-2Lx4-5h9m1RGFBNKmSlSgZMVwxZ1wGIpgHZq551dcfrrqw1glYMeN9grTMtlGHNhkuONVTlBi7I16PufupG3Bh0Od_Q7oMddXhpvbbt_xNnd-3WP7eNAJH_Lwt8fhMI_teEMbWjjSan0Q79FFtRlU22Kl_R63fok5-Cy_EOVKmqDFaZujlSJvgYA_Z_zXDWHvbcvtsz_AHmjJpB</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2544958395</pqid></control><display><type>article</type><title>Targeting HSF1 as a Therapeutic Strategy for Multiple Mechanisms of EGFR Inhibitor Resistance in EGFR Mutant Non-Small-Cell Lung Cancer</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>PubMed Central</source><creator>Lee, Sangah ; Jung, Jiyae ; Lee, Yu-Jin ; Kim, Seon-Kyu ; Kim, Jung-Ae ; Kim, Bo-Kyung ; Park, Kyung Chan ; Kwon, Byoung-Mog ; Han, Dong Cho</creator><creatorcontrib>Lee, Sangah ; Jung, Jiyae ; Lee, Yu-Jin ; Kim, Seon-Kyu ; Kim, Jung-Ae ; Kim, Bo-Kyung ; Park, Kyung Chan ; Kwon, Byoung-Mog ; Han, Dong Cho</creatorcontrib><description>Although EGFR-TKI treatment of NSCLC (non-small-cell lung cancer) patients often achieves profound initial responses, the efficacy is transient due to acquired resistance. Multiple receptor tyrosine kinase (RTK) pathways contribute to the resistance of NSCLC to first- and third-generation EGFR-TKIs, such as erlotinib and osimertinib. To identify potential targets for overcoming EGFR-TKI resistance, we performed a gene expression signature-based strategy using connectivity map (CMap) analysis. We generated erlotinib-resistant HCC827-ErlR cells, which showed resistance to erlotinib, gefitinib, osimertinib, and doxorubicin. A list of differentially expressed genes (DEGs) in HCC827-ErlR cells was generated and queried using CMap analysis. Analysis of the top 4 compounds from the CMap list suggested HSF1 as a potential target to overcome EGFR-TKI resistance. HSF1 inhibition by using HSF1 shRNAs or KRIBB11 decreased the expression of HSF1 downstream proteins, such as HSP70 and HSP27, and also decreased the expression of HSP90/HSP70/BAG3 client proteins, such as BCL2, MCL1, EGFR, MET, and AXL, causing apoptosis of EGFR-TKI-resistant cancer cells. Finally, we demonstrated the efficacy of the HSF1 inhibitor on PC9-ErlR cells expressing mutant EGFR (T790M) in vivo. Collectively, these findings support a targetable HSF1-(HSP90/HSP70/BAG3)-(BCL2/MCL1/EGFR/MET/AXL) pathway to overcome multiple mechanisms of EGFR-TKI resistance.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13122987</identifier><identifier>PMID: 34203709</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Antibodies ; Apoptosis ; Axl protein ; Binding sites ; c-Met protein ; Doxorubicin ; Emetine ; Epidermal growth factor receptors ; Gefitinib ; Gene expression ; Heat shock factors ; HSF1 protein ; Hsp27 protein ; Hsp70 protein ; Hsp90 protein ; Kinases ; Lung cancer ; Mcl-1 protein ; Mutants ; Mutation ; Non-small cell lung carcinoma ; Protein-tyrosine kinase receptors ; Proteins ; Small cell lung carcinoma ; Tumors</subject><ispartof>Cancers, 2021-06, Vol.13 (12), p.2987</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-7594030a50e0bb3328837f9f0b6b16b46ae3a9031f8e6a75929c08d171e6354d3</citedby><cites>FETCH-LOGICAL-c398t-7594030a50e0bb3328837f9f0b6b16b46ae3a9031f8e6a75929c08d171e6354d3</cites><orcidid>0000-0001-8870-2231 ; 0000-0001-5485-4843 ; 0000-0002-4176-5187 ; 0000-0003-0863-3008</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232331/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232331/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27911,27912,53778,53780</link.rule.ids></links><search><creatorcontrib>Lee, Sangah</creatorcontrib><creatorcontrib>Jung, Jiyae</creatorcontrib><creatorcontrib>Lee, Yu-Jin</creatorcontrib><creatorcontrib>Kim, Seon-Kyu</creatorcontrib><creatorcontrib>Kim, Jung-Ae</creatorcontrib><creatorcontrib>Kim, Bo-Kyung</creatorcontrib><creatorcontrib>Park, Kyung Chan</creatorcontrib><creatorcontrib>Kwon, Byoung-Mog</creatorcontrib><creatorcontrib>Han, Dong Cho</creatorcontrib><title>Targeting HSF1 as a Therapeutic Strategy for Multiple Mechanisms of EGFR Inhibitor Resistance in EGFR Mutant Non-Small-Cell Lung Cancer</title><title>Cancers</title><description>Although EGFR-TKI treatment of NSCLC (non-small-cell lung cancer) patients often achieves profound initial responses, the efficacy is transient due to acquired resistance. Multiple receptor tyrosine kinase (RTK) pathways contribute to the resistance of NSCLC to first- and third-generation EGFR-TKIs, such as erlotinib and osimertinib. To identify potential targets for overcoming EGFR-TKI resistance, we performed a gene expression signature-based strategy using connectivity map (CMap) analysis. We generated erlotinib-resistant HCC827-ErlR cells, which showed resistance to erlotinib, gefitinib, osimertinib, and doxorubicin. A list of differentially expressed genes (DEGs) in HCC827-ErlR cells was generated and queried using CMap analysis. Analysis of the top 4 compounds from the CMap list suggested HSF1 as a potential target to overcome EGFR-TKI resistance. HSF1 inhibition by using HSF1 shRNAs or KRIBB11 decreased the expression of HSF1 downstream proteins, such as HSP70 and HSP27, and also decreased the expression of HSP90/HSP70/BAG3 client proteins, such as BCL2, MCL1, EGFR, MET, and AXL, causing apoptosis of EGFR-TKI-resistant cancer cells. Finally, we demonstrated the efficacy of the HSF1 inhibitor on PC9-ErlR cells expressing mutant EGFR (T790M) in vivo. Collectively, these findings support a targetable HSF1-(HSP90/HSP70/BAG3)-(BCL2/MCL1/EGFR/MET/AXL) pathway to overcome multiple mechanisms of EGFR-TKI resistance.</description><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Axl protein</subject><subject>Binding sites</subject><subject>c-Met protein</subject><subject>Doxorubicin</subject><subject>Emetine</subject><subject>Epidermal growth factor receptors</subject><subject>Gefitinib</subject><subject>Gene expression</subject><subject>Heat shock factors</subject><subject>HSF1 protein</subject><subject>Hsp27 protein</subject><subject>Hsp70 protein</subject><subject>Hsp90 protein</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Mcl-1 protein</subject><subject>Mutants</subject><subject>Mutation</subject><subject>Non-small cell lung carcinoma</subject><subject>Protein-tyrosine kinase receptors</subject><subject>Proteins</subject><subject>Small cell lung carcinoma</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUFrGzEQhUVoSUKac66CXHrZRtLsrlaXQjFxErBbiN3zopVnbYVdyZW0gfyC_u3KcSht5qIR8_H0noaQK86-ACh2Y7QzGCIHLoRq5Ak5F0yKoq5V-eGf_oxcxvjEcgFwWctTcgalYCCZOie_1zpsMVm3pferOac6Uk3XOwx6j1Oyhq5S0Am3L7T3gS6nIdn9gHSJZqedjWOkvqe3d_NH-uB2trMpU48YbUwHc9S643A55Xui370rVqMehmKGw0AXU3529priE_nY6yHi5dt5QX7Ob9ez-2Lx4-5h9m1RGFBNKmSlSgZMVwxZ1wGIpgHZq551dcfrrqw1glYMeN9grTMtlGHNhkuONVTlBi7I16PufupG3Bh0Od_Q7oMddXhpvbbt_xNnd-3WP7eNAJH_Lwt8fhMI_teEMbWjjSan0Q79FFtRlU22Kl_R63fok5-Cy_EOVKmqDFaZujlSJvgYA_Z_zXDWHvbcvtsz_AHmjJpB</recordid><startdate>20210615</startdate><enddate>20210615</enddate><creator>Lee, Sangah</creator><creator>Jung, Jiyae</creator><creator>Lee, Yu-Jin</creator><creator>Kim, Seon-Kyu</creator><creator>Kim, Jung-Ae</creator><creator>Kim, Bo-Kyung</creator><creator>Park, Kyung Chan</creator><creator>Kwon, Byoung-Mog</creator><creator>Han, Dong Cho</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</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><orcidid>https://orcid.org/0000-0001-8870-2231</orcidid><orcidid>https://orcid.org/0000-0001-5485-4843</orcidid><orcidid>https://orcid.org/0000-0002-4176-5187</orcidid><orcidid>https://orcid.org/0000-0003-0863-3008</orcidid></search><sort><creationdate>20210615</creationdate><title>Targeting HSF1 as a Therapeutic Strategy for Multiple Mechanisms of EGFR Inhibitor Resistance in EGFR Mutant Non-Small-Cell Lung Cancer</title><author>Lee, Sangah ; Jung, Jiyae ; Lee, Yu-Jin ; Kim, Seon-Kyu ; Kim, Jung-Ae ; Kim, Bo-Kyung ; Park, Kyung Chan ; Kwon, Byoung-Mog ; Han, Dong Cho</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-7594030a50e0bb3328837f9f0b6b16b46ae3a9031f8e6a75929c08d171e6354d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Axl protein</topic><topic>Binding sites</topic><topic>c-Met protein</topic><topic>Doxorubicin</topic><topic>Emetine</topic><topic>Epidermal growth factor receptors</topic><topic>Gefitinib</topic><topic>Gene expression</topic><topic>Heat shock factors</topic><topic>HSF1 protein</topic><topic>Hsp27 protein</topic><topic>Hsp70 protein</topic><topic>Hsp90 protein</topic><topic>Kinases</topic><topic>Lung cancer</topic><topic>Mcl-1 protein</topic><topic>Mutants</topic><topic>Mutation</topic><topic>Non-small cell lung carcinoma</topic><topic>Protein-tyrosine kinase receptors</topic><topic>Proteins</topic><topic>Small cell lung carcinoma</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Sangah</creatorcontrib><creatorcontrib>Jung, Jiyae</creatorcontrib><creatorcontrib>Lee, Yu-Jin</creatorcontrib><creatorcontrib>Kim, Seon-Kyu</creatorcontrib><creatorcontrib>Kim, Jung-Ae</creatorcontrib><creatorcontrib>Kim, Bo-Kyung</creatorcontrib><creatorcontrib>Park, Kyung Chan</creatorcontrib><creatorcontrib>Kwon, Byoung-Mog</creatorcontrib><creatorcontrib>Han, Dong Cho</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</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 (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Sangah</au><au>Jung, Jiyae</au><au>Lee, Yu-Jin</au><au>Kim, Seon-Kyu</au><au>Kim, Jung-Ae</au><au>Kim, Bo-Kyung</au><au>Park, Kyung Chan</au><au>Kwon, Byoung-Mog</au><au>Han, Dong Cho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting HSF1 as a Therapeutic Strategy for Multiple Mechanisms of EGFR Inhibitor Resistance in EGFR Mutant Non-Small-Cell Lung Cancer</atitle><jtitle>Cancers</jtitle><date>2021-06-15</date><risdate>2021</risdate><volume>13</volume><issue>12</issue><spage>2987</spage><pages>2987-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Although EGFR-TKI treatment of NSCLC (non-small-cell lung cancer) patients often achieves profound initial responses, the efficacy is transient due to acquired resistance. Multiple receptor tyrosine kinase (RTK) pathways contribute to the resistance of NSCLC to first- and third-generation EGFR-TKIs, such as erlotinib and osimertinib. To identify potential targets for overcoming EGFR-TKI resistance, we performed a gene expression signature-based strategy using connectivity map (CMap) analysis. We generated erlotinib-resistant HCC827-ErlR cells, which showed resistance to erlotinib, gefitinib, osimertinib, and doxorubicin. A list of differentially expressed genes (DEGs) in HCC827-ErlR cells was generated and queried using CMap analysis. Analysis of the top 4 compounds from the CMap list suggested HSF1 as a potential target to overcome EGFR-TKI resistance. HSF1 inhibition by using HSF1 shRNAs or KRIBB11 decreased the expression of HSF1 downstream proteins, such as HSP70 and HSP27, and also decreased the expression of HSP90/HSP70/BAG3 client proteins, such as BCL2, MCL1, EGFR, MET, and AXL, causing apoptosis of EGFR-TKI-resistant cancer cells. Finally, we demonstrated the efficacy of the HSF1 inhibitor on PC9-ErlR cells expressing mutant EGFR (T790M) in vivo. Collectively, these findings support a targetable HSF1-(HSP90/HSP70/BAG3)-(BCL2/MCL1/EGFR/MET/AXL) pathway to overcome multiple mechanisms of EGFR-TKI resistance.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>34203709</pmid><doi>10.3390/cancers13122987</doi><orcidid>https://orcid.org/0000-0001-8870-2231</orcidid><orcidid>https://orcid.org/0000-0001-5485-4843</orcidid><orcidid>https://orcid.org/0000-0002-4176-5187</orcidid><orcidid>https://orcid.org/0000-0003-0863-3008</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2021-06, Vol.13 (12), p.2987 |
| issn | 2072-6694 2072-6694 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8232331 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Antibodies Apoptosis Axl protein Binding sites c-Met protein Doxorubicin Emetine Epidermal growth factor receptors Gefitinib Gene expression Heat shock factors HSF1 protein Hsp27 protein Hsp70 protein Hsp90 protein Kinases Lung cancer Mcl-1 protein Mutants Mutation Non-small cell lung carcinoma Protein-tyrosine kinase receptors Proteins Small cell lung carcinoma Tumors |
| title | Targeting HSF1 as a Therapeutic Strategy for Multiple Mechanisms of EGFR Inhibitor Resistance in EGFR Mutant Non-Small-Cell Lung Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T14%3A40%3A26IST&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=Targeting%20HSF1%20as%20a%20Therapeutic%20Strategy%20for%20Multiple%20Mechanisms%20of%20EGFR%20Inhibitor%20Resistance%20in%20EGFR%20Mutant%20Non-Small-Cell%20Lung%20Cancer&rft.jtitle=Cancers&rft.au=Lee,%20Sangah&rft.date=2021-06-15&rft.volume=13&rft.issue=12&rft.spage=2987&rft.pages=2987-&rft.issn=2072-6694&rft.eissn=2072-6694&rft_id=info:doi/10.3390/cancers13122987&rft_dat=%3Cproquest_pubme%3E2544958395%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=2544958395&rft_id=info:pmid/34203709&rfr_iscdi=true |