{"created":"2023-07-27T06:53:26.748350+00:00","id":48141,"links":{},"metadata":{"_buckets":{"deposit":"34c03ae8-70b6-451d-a282-679ac531131a"},"_deposit":{"created_by":18,"id":"48141","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"48141"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00048141","sets":["2812:2813:2815"]},"author_link":["85784","85785"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-06-07","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"5p.","bibliographicVolumeNumber":"2016-04-01 - 2019-03-31","bibliographic_titles":[{"bibliographic_title":"平成30(2018)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"2018 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"KRASの下流タンパクであるMEKの阻害薬は、上流の受容体を活性化するため治療効果を発揮できない。KRAS変異肺がんを上皮間葉移行状態（EMT）に基づき2種類に分類し、活性化される受容体が、上皮系の性質を示す腫瘍ではERBB3、間葉系の性質を示す腫瘍ではFGFR1であることを明らかにした。それぞれの受容体に対する阻害薬とMEK阻害薬の併用について検討し、マウスゼノグラフトモデルおよび患者検体由来ゼノグラフトモデルにおいて有効性を示した。さらにEMTの状態に関わらずMEK阻害薬と併用効果を示す治療標的を探索し、受容体とKRASの間に位置するアダプタータンパクであるSHP2を同定した。","subitem_description_type":"Abstract"},{"subitem_description":"Whereas the mitogen-activated protein kinase (MAPK) is a well-known effector pathway of KRAS, blocking this pathway with clinically-available MAPK inhibitors is relatively ineffective. We identified that epithelial-to-mesenchymal transition (EMT) rewires the expression of receptor tyrosine kinases, leading to differential feedback activation of the MAPK pathway following MEK inhibition. In epithelial-like KRAS mutant lung cancers, this feedback was attributed to ERBB3. In contrast, in mesenchymal-like KRAS mutant lung cancers, FGFR1 was dominantly expressed but suppressed by the negative regulator sprouty proteins; MEK inhibition led to de-repression of SPRY4 and subsequent FGFR1-mediated re-activation of MEK. Therapeutically, the combination of MEK inhibitor and FGFR inhibitor induced cell death in vitro and tumor regressions in vivo. We established the rationale and a therapeutic approach to treat KRAS mutant lung cancers effectively. ","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:16K07164, 研究期間(年度):2016-04-01 - 2019-03-31","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「上皮間葉移行状態に基づいたKRAS変異肺がんに対する治療開発」課題番号16K07164\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） \n（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-16K07164/16K07164seika/)を加工して作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00054463","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":" 愛知県がんセンター(研究所) / 金沢大学がん進展制御研究所"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=00645145"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=00645145","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16K07164/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16K07164/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-16K07164/16K07164seika/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-16K07164/16K07164seika/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-04-23"}],"displaytype":"detail","filename":"CA-PR-EBI-H-kaken 2019-5p.pdf","filesize":[{"value":"607.5 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-EBI-H-kaken 2019-5p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/48141/files/CA-PR-EBI-H-kaken 2019-5p.pdf"},"version_id":"d0740e4e-8077-480d-a6f9-aa1ada401be7"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"上皮間葉移行状態に基づいたKRAS変異肺がんに対する治療開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"上皮間葉移行状態に基づいたKRAS変異肺がんに対する治療開発"},{"subitem_title":"Development of target therapy against KRAS mutant lung cancer stratified by EMT status","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2815"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-04-23"},"publish_date":"2020-04-23","publish_status":"0","recid":"48141","relation_version_is_last":true,"title":["上皮間葉移行状態に基づいたKRAS変異肺がんに対する治療開発"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T13:36:49.069409+00:00"}