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