{"created":"2023-07-27T06:53:26.816661+00:00","id":48142,"links":{},"metadata":{"_buckets":{"deposit":"790608f7-e9c7-4bcb-8b20-31706ce78a95"},"_deposit":{"created_by":18,"id":"48142","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"48142"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00048142","sets":["2812:2813:3929"]},"author_link":["2728","47736"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-05-18","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"11p.","bibliographicVolumeNumber":"2016-2018","bibliographic_titles":[{"bibliographic_title":"令和1(2019)年度 科学研究費補助金 国際共同研究加速基金(国際共同研究強化) 研究成果報告書"},{"bibliographic_title":"2019 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変異腫瘍が上皮間葉移行状態により2種類に分類できることを明らかにした。ERKパスウエイの抑制は、上流受容体のフィードバック活性化を誘導するが、活性化される受容体が上皮型ではERBB3、間葉型ではFGFR1であり、MEK阻害薬と受容体阻害薬の併用が、それぞれの性質を示す腫瘍の治療に有効であること示した。また、上皮間葉移行状態に関わらずMEK阻害薬と併用効果を示す標的としてSHP2を同定した。近年開発の進むKRAS G12C変異直接阻害薬について、感受性や耐性規定因子を解析・同定した。さらに本課題を通じ新たな国際共同研究を展開しBRAF遺伝子変異腫瘍に対する個別化治療の提唱を行った。","subitem_description_type":"Abstract"},{"subitem_description":"We identified epithelial-to-mesenchymal transition (EMT) rewires the expression of receptor tyrosine kinases (RTKs), leading to differential feedback activation of the ERK pathway following MEK inhibition in KRAS mutant cancer. In epithelial-like cancers, this feedback was attributed to ERBB3-mediated activation of MEK and AKT. In contrast, in mesenchymal-like cancers, FGFR1 was dominantly expressed but suppressed by the negative regulator Sprouty proteins; MEK inhibition led to repression of SPRY4 and subsequent FGFR1-mediated reactivation of MEK and AKT. Therapeutically, the combination of a MEK inhibitor with respective RTK inhibitors induced cell death in vitro and tumor regressions in vivo. We also functionally characterized BRAF mutant cancers by an international collaboration. Collectively, we have established the rationale and a therapeutic approach to treat KRAS-mutant lung cancers based on EMT status, and BRAF mutant cancers based on its functional classification.","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:15KK0303, 研究期間(年度):2016-2018","subitem_description_type":"Other"},{"subitem_description":"出典：「PI3 KおよびERKパスウエイを標的としたKRAS変異腫瘍に対する新規治療開発 (国際共同研究強化)」研究成果報告書　課題番号15KK0303\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-15KK0303/15KK0303seika/)を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"愛知県がんセンター / 金沢大学がん進展制御研究所","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00054464","subitem_identifier_reg_type":"JaLC"}]},"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-15KK0303/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15KK0303/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-15KK0303/15KK0303seika/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-15KK0303/15KK0303seika/","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":"2021-05-14"}],"displaytype":"detail","filename":"CA-PR-EBI-H-kaken 2020-11p.pdf","filesize":[{"value":"899.2 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-EBI-H-kaken 2020-11p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/48142/files/CA-PR-EBI-H-kaken 2020-11p.pdf"},"version_id":"967cf0e4-24e2-446e-9c9c-a4c808855c11"}]},"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":"PI3 KおよびERKパスウエイを標的としたKRAS変異腫瘍に対する新規治療開発 (国際共同研究強化)","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"PI3 KおよびERKパスウエイを標的としたKRAS変異腫瘍に対する新規治療開発 (国際共同研究強化)"},{"subitem_title":"Develop novel therapeutics against KRAS mutant cancer by regulating PI3K and ERK signal(Fostering Joint International Research)","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["3929"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-05-14"},"publish_date":"2021-05-14","publish_status":"0","recid":"48142","relation_version_is_last":true,"title":["PI3 KおよびERKパスウエイを標的としたKRAS変異腫瘍に対する新規治療開発 (国際共同研究強化)"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:10:23.218813+00:00"}