Establishment of organoid-based drug screening testing facilitates precision chemotherapy for pancreatic cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07739
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Keio University
• Principal Investigator: IWASAKI Eisuke 慶應義塾大学, 医学部(信濃町), 講師 (10366172)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 膵臓がん / オルガノイド

Outline of Final Research Achievements

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.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

胆膵悪性腫瘍患者は年々増加し、抗癌剤感受性も低く, 最も難治性の悪性腫瘍に分類されており, 革新的な診断技術や治療方法の開発が求められている. 進行した状態で発見されることが多く, 多くの患者は化学療法となる．化学療法は多数の患者による臨床試験結果に基づき「画一的に」行われるため,患者ごとに治療効果は異なる. 同じ癌腫であっても変異の違いなどから抗癌剤の応答性が異なることが原因と考えられ、「オーダーメイド」治療の実現が望まれている. 今回は胆膵腫瘍から作成した癌オルガノイドを用いて薬剤感受性試験の開発をすすめ、短期間でその結果を得られる新規手法を開発したことから、学術的、社会的意義は高い。