AXL degradation in combination with EGFR-TKI can delay and overcome acquired resistance in human non-small cell lung cancer cells
Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. AXL has been reported to mediate EGFR-TKIs. Recently, third generation EGFR-TKI osimertinib has been approved and...
Gespeichert in:
| Veröffentlicht in: | Cell death & disease 2019-05, Vol.10 (5), p.361-361, Article 361 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 361 |
|---|---|
| container_issue | 5 |
| container_start_page | 361 |
| container_title | Cell death & disease |
| container_volume | 10 |
| creator | Kim, Donghwa Bach, Duc-Hiep Fan, Yan-Hua Luu, Thi-Thu-Trang Hong, Ji-Young Park, Hyen Joo Lee, Sang Kook |
| description | Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. AXL has been reported to mediate EGFR-TKIs. Recently, third generation EGFR-TKI osimertinib has been approved and yet its acquired resistance mechanism is not clearly understood. We found that AXL is involved in both gefitinib and osimertinib resistance using in vitro and in vivo model. In addition, AXL overexpression was correlated with extended protein degradation rate. We demonstrate targeting AXL degradation is an alternative route to restore EGFR-TKIs sensitivity. We confirmed that the combination effect of YD, an AXL degrader, and EGFR-TKIs can delay or overcome EGFR-TKIs-driven resistance in EGFR-mutant NSCLC cells, xenograft tumors, and patient-derived xenograft (PDX) models. Therefore, combination of EGFR-TKI and AXL degrader is a potentially effective treatment strategy for overcoming and delaying acquired resistance in NSCLC. |
| doi_str_mv | 10.1038/s41419-019-1601-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6494839</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2218264609</sourcerecordid><originalsourceid>FETCH-LOGICAL-c470t-2b4fcb82fe1494cd3fe479401385b62d3730d135c03991f3f59774e752d4afdd3</originalsourceid><addsrcrecordid>eNp1kUtLHjEUhkNRqqg_oJsS6MbN1Nzmkk1BxBv9oFAsdBcyyZnvi8wkmswoLv3nZhyrttBAruc578nhRegTJV8p4c1RElRQWZA8aUVoUX1Au4wIWoimkVvvzjvoIKVrkgfnhJXVR7TDKRG8bOpd9Hj8e4UtrKO2enTBY-exCUPr_HK9d-MGn56f_Syuvl9io32Ge_2Atbc43EHMLGBtbicXweIIyaVRewOzzmYaMu-DL9Kg-x4byEs_-fWsYyA-P6R9tN3pPsHBy76Hfp2dXp1cFKsf55cnx6vCiJqMBWtFZ9qGdUCFFMbyDkQtBaG8KduKWV5zYikvDeFS0o53paxrAXXJrNCdtXwPfVt0b6Z2AGvAj1H36ia6QccHFbRTf0e826h1uFNVrtdwmQUOXwRiuJ0gjWpwaW5BewhTUozRRkpZlnVGv_yDXocp-tzeM8UqUZFZkC6UiSGlCN3rZyhRs8dq8Vhlj9Xssapyzuf3Xbxm_HE0A2wBUg75NcS30v9XfQIO1bIt</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2218264609</pqid></control><display><type>article</type><title>AXL degradation in combination with EGFR-TKI can delay and overcome acquired resistance in human non-small cell lung cancer cells</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Springer Nature OA Free Journals</source><creator>Kim, Donghwa ; Bach, Duc-Hiep ; Fan, Yan-Hua ; Luu, Thi-Thu-Trang ; Hong, Ji-Young ; Park, Hyen Joo ; Lee, Sang Kook</creator><creatorcontrib>Kim, Donghwa ; Bach, Duc-Hiep ; Fan, Yan-Hua ; Luu, Thi-Thu-Trang ; Hong, Ji-Young ; Park, Hyen Joo ; Lee, Sang Kook</creatorcontrib><description>Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. AXL has been reported to mediate EGFR-TKIs. Recently, third generation EGFR-TKI osimertinib has been approved and yet its acquired resistance mechanism is not clearly understood. We found that AXL is involved in both gefitinib and osimertinib resistance using in vitro and in vivo model. In addition, AXL overexpression was correlated with extended protein degradation rate. We demonstrate targeting AXL degradation is an alternative route to restore EGFR-TKIs sensitivity. We confirmed that the combination effect of YD, an AXL degrader, and EGFR-TKIs can delay or overcome EGFR-TKIs-driven resistance in EGFR-mutant NSCLC cells, xenograft tumors, and patient-derived xenograft (PDX) models. Therefore, combination of EGFR-TKI and AXL degrader is a potentially effective treatment strategy for overcoming and delaying acquired resistance in NSCLC.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-019-1601-6</identifier><identifier>PMID: 31043587</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/109 ; 13/51 ; 13/89 ; 13/95 ; 14/19 ; 38 ; 38/77 ; 38/90 ; 59 ; 59/5 ; 631/154/556 ; 631/67/1612/1350 ; 64 ; 64/60 ; 82 ; 82/80 ; 96 ; Acrylamides - pharmacology ; Aniline Compounds - pharmacology ; Animals ; Antibodies ; Antineoplastic Agents - pharmacology ; Axl protein ; Biochemistry ; Biomedical and Life Sciences ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - pathology ; Cell Biology ; Cell Culture ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Drug Resistance, Neoplasm - drug effects ; Drug Resistance, Neoplasm - genetics ; Drugs, Chinese Herbal - pharmacology ; Epidermal growth factor ; Epidermal growth factor receptors ; ErbB Receptors - antagonists & inhibitors ; ErbB Receptors - genetics ; ErbB Receptors - metabolism ; Female ; Gefitinib ; Gefitinib - pharmacology ; Gene Expression Regulation, Neoplastic ; Immunology ; Kinases ; Life Sciences ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Male ; Mice, Nude ; Non-small cell lung carcinoma ; Protein Kinase Inhibitors - pharmacology ; Protein-tyrosine kinase ; Proteolysis - drug effects ; Proto-Oncogene Proteins - antagonists & inhibitors ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - metabolism ; Receptor Protein-Tyrosine Kinases - antagonists & inhibitors ; Receptor Protein-Tyrosine Kinases - genetics ; Receptor Protein-Tyrosine Kinases - metabolism ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; Signal Transduction ; Terpenes - pharmacology ; Tumor Burden - drug effects ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>Cell death & disease, 2019-05, Vol.10 (5), p.361-361, Article 361</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019. 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-c470t-2b4fcb82fe1494cd3fe479401385b62d3730d135c03991f3f59774e752d4afdd3</citedby><cites>FETCH-LOGICAL-c470t-2b4fcb82fe1494cd3fe479401385b62d3730d135c03991f3f59774e752d4afdd3</cites><orcidid>0000-0002-4306-7024</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/PMC6494839/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494839/$$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/31043587$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Donghwa</creatorcontrib><creatorcontrib>Bach, Duc-Hiep</creatorcontrib><creatorcontrib>Fan, Yan-Hua</creatorcontrib><creatorcontrib>Luu, Thi-Thu-Trang</creatorcontrib><creatorcontrib>Hong, Ji-Young</creatorcontrib><creatorcontrib>Park, Hyen Joo</creatorcontrib><creatorcontrib>Lee, Sang Kook</creatorcontrib><title>AXL degradation in combination with EGFR-TKI can delay and overcome acquired resistance in human non-small cell lung cancer cells</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. AXL has been reported to mediate EGFR-TKIs. Recently, third generation EGFR-TKI osimertinib has been approved and yet its acquired resistance mechanism is not clearly understood. We found that AXL is involved in both gefitinib and osimertinib resistance using in vitro and in vivo model. In addition, AXL overexpression was correlated with extended protein degradation rate. We demonstrate targeting AXL degradation is an alternative route to restore EGFR-TKIs sensitivity. We confirmed that the combination effect of YD, an AXL degrader, and EGFR-TKIs can delay or overcome EGFR-TKIs-driven resistance in EGFR-mutant NSCLC cells, xenograft tumors, and patient-derived xenograft (PDX) models. Therefore, combination of EGFR-TKI and AXL degrader is a potentially effective treatment strategy for overcoming and delaying acquired resistance in NSCLC.</description><subject>13/1</subject><subject>13/109</subject><subject>13/51</subject><subject>13/89</subject><subject>13/95</subject><subject>14/19</subject><subject>38</subject><subject>38/77</subject><subject>38/90</subject><subject>59</subject><subject>59/5</subject><subject>631/154/556</subject><subject>631/67/1612/1350</subject><subject>64</subject><subject>64/60</subject><subject>82</subject><subject>82/80</subject><subject>96</subject><subject>Acrylamides - pharmacology</subject><subject>Aniline Compounds - pharmacology</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Axl protein</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>ErbB Receptors - antagonists & inhibitors</subject><subject>ErbB Receptors - genetics</subject><subject>ErbB Receptors - metabolism</subject><subject>Female</subject><subject>Gefitinib</subject><subject>Gefitinib - pharmacology</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Immunology</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Mice, Nude</subject><subject>Non-small cell lung carcinoma</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein-tyrosine kinase</subject><subject>Proteolysis - drug effects</subject><subject>Proto-Oncogene Proteins - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Receptor Protein-Tyrosine Kinases - antagonists & inhibitors</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Receptor Protein-Tyrosine Kinases - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Signal Transduction</subject><subject>Terpenes - pharmacology</subject><subject>Tumor Burden - drug effects</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUtLHjEUhkNRqqg_oJsS6MbN1Nzmkk1BxBv9oFAsdBcyyZnvi8wkmswoLv3nZhyrttBAruc578nhRegTJV8p4c1RElRQWZA8aUVoUX1Au4wIWoimkVvvzjvoIKVrkgfnhJXVR7TDKRG8bOpd9Hj8e4UtrKO2enTBY-exCUPr_HK9d-MGn56f_Syuvl9io32Ge_2Atbc43EHMLGBtbicXweIIyaVRewOzzmYaMu-DL9Kg-x4byEs_-fWsYyA-P6R9tN3pPsHBy76Hfp2dXp1cFKsf55cnx6vCiJqMBWtFZ9qGdUCFFMbyDkQtBaG8KduKWV5zYikvDeFS0o53paxrAXXJrNCdtXwPfVt0b6Z2AGvAj1H36ia6QccHFbRTf0e826h1uFNVrtdwmQUOXwRiuJ0gjWpwaW5BewhTUozRRkpZlnVGv_yDXocp-tzeM8UqUZFZkC6UiSGlCN3rZyhRs8dq8Vhlj9Xssapyzuf3Xbxm_HE0A2wBUg75NcS30v9XfQIO1bIt</recordid><startdate>20190501</startdate><enddate>20190501</enddate><creator>Kim, Donghwa</creator><creator>Bach, Duc-Hiep</creator><creator>Fan, Yan-Hua</creator><creator>Luu, Thi-Thu-Trang</creator><creator>Hong, Ji-Young</creator><creator>Park, Hyen Joo</creator><creator>Lee, Sang Kook</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</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><orcidid>https://orcid.org/0000-0002-4306-7024</orcidid></search><sort><creationdate>20190501</creationdate><title>AXL degradation in combination with EGFR-TKI can delay and overcome acquired resistance in human non-small cell lung cancer cells</title><author>Kim, Donghwa ; Bach, Duc-Hiep ; Fan, Yan-Hua ; Luu, Thi-Thu-Trang ; Hong, Ji-Young ; Park, Hyen Joo ; Lee, Sang Kook</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-2b4fcb82fe1494cd3fe479401385b62d3730d135c03991f3f59774e752d4afdd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/1</topic><topic>13/109</topic><topic>13/51</topic><topic>13/89</topic><topic>13/95</topic><topic>14/19</topic><topic>38</topic><topic>38/77</topic><topic>38/90</topic><topic>59</topic><topic>59/5</topic><topic>631/154/556</topic><topic>631/67/1612/1350</topic><topic>64</topic><topic>64/60</topic><topic>82</topic><topic>82/80</topic><topic>96</topic><topic>Acrylamides - pharmacology</topic><topic>Aniline Compounds - pharmacology</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Axl protein</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor receptors</topic><topic>ErbB Receptors - antagonists & inhibitors</topic><topic>ErbB Receptors - genetics</topic><topic>ErbB Receptors - metabolism</topic><topic>Female</topic><topic>Gefitinib</topic><topic>Gefitinib - pharmacology</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Immunology</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Mice, Nude</topic><topic>Non-small cell lung carcinoma</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein-tyrosine kinase</topic><topic>Proteolysis - drug effects</topic><topic>Proto-Oncogene Proteins - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Receptor Protein-Tyrosine Kinases - antagonists & inhibitors</topic><topic>Receptor Protein-Tyrosine Kinases - genetics</topic><topic>Receptor Protein-Tyrosine Kinases - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Signal Transduction</topic><topic>Terpenes - pharmacology</topic><topic>Tumor Burden - drug effects</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Donghwa</creatorcontrib><creatorcontrib>Bach, Duc-Hiep</creatorcontrib><creatorcontrib>Fan, Yan-Hua</creatorcontrib><creatorcontrib>Luu, Thi-Thu-Trang</creatorcontrib><creatorcontrib>Hong, Ji-Young</creatorcontrib><creatorcontrib>Park, Hyen Joo</creatorcontrib><creatorcontrib>Lee, Sang Kook</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</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>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 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>Science Database</collection><collection>Biological Science 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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Donghwa</au><au>Bach, Duc-Hiep</au><au>Fan, Yan-Hua</au><au>Luu, Thi-Thu-Trang</au><au>Hong, Ji-Young</au><au>Park, Hyen Joo</au><au>Lee, Sang Kook</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AXL degradation in combination with EGFR-TKI can delay and overcome acquired resistance in human non-small cell lung cancer cells</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2019-05-01</date><risdate>2019</risdate><volume>10</volume><issue>5</issue><spage>361</spage><epage>361</epage><pages>361-361</pages><artnum>361</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. AXL has been reported to mediate EGFR-TKIs. Recently, third generation EGFR-TKI osimertinib has been approved and yet its acquired resistance mechanism is not clearly understood. We found that AXL is involved in both gefitinib and osimertinib resistance using in vitro and in vivo model. In addition, AXL overexpression was correlated with extended protein degradation rate. We demonstrate targeting AXL degradation is an alternative route to restore EGFR-TKIs sensitivity. We confirmed that the combination effect of YD, an AXL degrader, and EGFR-TKIs can delay or overcome EGFR-TKIs-driven resistance in EGFR-mutant NSCLC cells, xenograft tumors, and patient-derived xenograft (PDX) models. Therefore, combination of EGFR-TKI and AXL degrader is a potentially effective treatment strategy for overcoming and delaying acquired resistance in NSCLC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31043587</pmid><doi>10.1038/s41419-019-1601-6</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-4306-7024</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-4889 |
| ispartof | Cell death & disease, 2019-05, Vol.10 (5), p.361-361, Article 361 |
| issn | 2041-4889 2041-4889 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6494839 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Springer Nature OA Free Journals |
| subjects | 13/1 13/109 13/51 13/89 13/95 14/19 38 38/77 38/90 59 59/5 631/154/556 631/67/1612/1350 64 64/60 82 82/80 96 Acrylamides - pharmacology Aniline Compounds - pharmacology Animals Antibodies Antineoplastic Agents - pharmacology Axl protein Biochemistry Biomedical and Life Sciences Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology Cell Biology Cell Culture Cell Line, Tumor Cell Proliferation - drug effects Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Drugs, Chinese Herbal - pharmacology Epidermal growth factor Epidermal growth factor receptors ErbB Receptors - antagonists & inhibitors ErbB Receptors - genetics ErbB Receptors - metabolism Female Gefitinib Gefitinib - pharmacology Gene Expression Regulation, Neoplastic Immunology Kinases Life Sciences Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Male Mice, Nude Non-small cell lung carcinoma Protein Kinase Inhibitors - pharmacology Protein-tyrosine kinase Proteolysis - drug effects Proto-Oncogene Proteins - antagonists & inhibitors Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Receptor Protein-Tyrosine Kinases - antagonists & inhibitors Receptor Protein-Tyrosine Kinases - genetics Receptor Protein-Tyrosine Kinases - metabolism RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Signal Transduction Terpenes - pharmacology Tumor Burden - drug effects Xenograft Model Antitumor Assays Xenografts |
| title | AXL degradation in combination with EGFR-TKI can delay and overcome acquired resistance in human non-small cell lung cancer cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T05%3A24%3A08IST&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=AXL%20degradation%20in%20combination%20with%20EGFR-TKI%20can%20delay%20and%20overcome%20acquired%20resistance%20in%20human%20non-small%20cell%20lung%20cancer%20cells&rft.jtitle=Cell%20death%20&%20disease&rft.au=Kim,%20Donghwa&rft.date=2019-05-01&rft.volume=10&rft.issue=5&rft.spage=361&rft.epage=361&rft.pages=361-361&rft.artnum=361&rft.issn=2041-4889&rft.eissn=2041-4889&rft_id=info:doi/10.1038/s41419-019-1601-6&rft_dat=%3Cproquest_pubme%3E2218264609%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=2218264609&rft_id=info:pmid/31043587&rfr_iscdi=true |