2023 Fiscal Year Final Research Report

Organoid Culture for Next Generation Personalized Medicine against Colorectal Cancer

Research Project

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Project/Area Number	21K08679
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Tohoku University
Principal Investigator	Karasawa Hideaki 東北大学, 大学病院, 助教 (30547401)
Co-Investigator(Kenkyū-buntansha)	大沼忍東北大学, 医学系研究科, 准教授 (70451565) 山村明寛東北大学, 大学病院, 助教 (30814678) 黒羽正剛東北大学, 医学系研究科, 大学院非常勤講師 (70709469) 小峰啓吾東北大学, 大学病院, 助教 (10725807) 岡村容伸東北大学, 未来型医療創成センター, 助教 (00837495)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	オルガノイド / 大腸癌 / MAPK / ERK阻害薬
Outline of Final Research Achievements	MAPK pathway plays an important role in the colorectal cancer (CRC), being supposed to be activated by the gene mutations. Although the inhibitors of ERK have demonstrated efficacy in the cells with the BRAF or KRAS mutations, a clinical response is not always associated with the molecular signature. The patient-derived organoids (PDO) have emerged as a powerful tool to study cancer. The present study aims to analyze the association between the molecular characteristics and sensitivity to the ERK inhibitor (SCH772984) in PDO. In the drug sensitivity test for PDO, 6 out of 7 cases with either BRAF or KRAS mutations showed sensitivity to the SCH772984, while 5 out of 6 cases of both BRAF and KRAS wild-types were resistant. The results of this study suggested that the molecular status of the clinical specimens are likely to represent the sensitivity in the PDOs. PDO might be able to complement the limitations of the gene panel and have the potential to provide a novel precision medicine.
Free Research Field	大腸癌
Academic Significance and Societal Importance of the Research Achievements	NGSによって包括的に遺伝子変異を把握する個別化医療は、近年急速に発達してきているが、遺伝子変異のみによるアプローチは予測にとどまり、NGSを用いた薬剤選択とオルガノイドにおける薬剤反応は必ずしも一致しないことが分かった。オルガノイド培養を用いた感受性試験ははNGSの弱点を補い、より精度の高い個別化医療を実現するために有用な手法となる可能性があると考えらえた。