胆膵がんオルガノイドをもちいた薬剤感受性試験確立と薬剤応答性メカニズムの解明

Material type: 文書・図像類

Author: 岩崎, 栄典ほか

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Publication date: 2021

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Note (General)：: type:text膵臓がんオルガノイドバンクをもちいた薬剤感受性試験の結果、Tp53変異存在下でNutlin3aに対する薬剤耐性があることが再現され妥当性が示された。また、オルガノイドバンク40例の臨床情報と既存薬の感受性試験にて、PTXまたはGEMの高いIC50値は、全体的な生存率低下と有意に関連...

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科研費研究者番号 : 10366172

科研費研究者番号 : 70365245

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Material Type: 文書・図像類
Title: 胆膵がんオルガノイドをもちいた薬剤感受性試験確立と薬剤応答性メカニズムの解明
Author/Editor: 岩崎, 栄典
佐藤, 俊朗
Author Heading: 岩崎, 栄典
佐藤, 俊朗
Publication Date: 2021
Publication Date (W3CDTF): 2021
Alternative Title: タンスイガンオルガノイドオモチイタヤクザイカンジュセイシケンカクリツトヤクザイオウトウセイメカニズムノカイメイ
Tansuigan oruganoido o mochiita yakuzai kanjusei shiken kakuritsu to yakuzai ōtōsei mekanizumu no kaimei
Establishment of organoid-based drug screening testing facilitates precision chemotherapy for pancreatic cancer
Periodical title: 科学研究費補助金研究成果報告書
Text Language Code: jpn
eng
Subject Heading: 膵臓がん,オルガノイド
Target Audience: 一般
Note (General): type:text
膵臓がんオルガノイドバンクをもちいた薬剤感受性試験の結果、Tp53変異存在下でNutlin3aに対する薬剤耐性があることが再現され妥当性が示された。また、オルガノイドバンク40例の臨床情報と既存薬の感受性試験にて、PTXまたはGEMの高いIC50値は、全体的な生存率低下と有意に関連した。薬剤感受性試験の短縮に向けて、Paclitaxelとtubulin形成異常、フローサイトメトリーを用いた細胞周期分布変化を解析するSnap-organoid testを確立し、3週間以内に実行することを可能とした。高悪性度がんに迅速な精密医療を提供できる可能性が示された。 The drug sensitivity of patient derived PDAC organoids recapitulated known pharmacogenetic associations using their exome sequencing data showed that organoids with TP53 mutation were more resistant to Nutlin-3a than TP53-wild-type organoids. Our system seems to be a valid platform for drug screening. We compared organoid drug sensitivity with clinical response of 40 patients. A high IC50 value for PTX or GEM in patient-derived organoids was significantly associated with an inferior overall survival of the donor patients. To rapidly identify potential responders, we further established a cell cycle-based assay that predicts drug response within 1-2 days following drug treatment. Snap-organoid test applying this technique revealed that screening procedures could be done in 3 weeks. Our results shows not only the potential of organoid-based drug screening in predicting clinical response but also the benefit of Snap-organoid test in streamlining precision treatment for aggressive cancers.
研究種目 : 基盤研究 (C) (一般) 研究期間 : 2019～2021 課題番号 : 19K07739 研究分野 : 消化器内科学
Access Restrictions: 限定公開
Related Material: 科研費研究者番号 : 10366172
科研費研究者番号 : 70365245
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 慶應義塾大学 : 慶應義塾大学学術情報リポジトリ