Search for new therapeutic target against cancer stem cells using intestinal-/gastric type gastric cancer organoid

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07017
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: National Cancer Center Japan (2020); Hiroshima University (2018-2019)
• Principal Investigator: Naoya Sakamoto 国立研究開発法人国立がん研究センター, 先端医療開発センター, ユニット長 (20571798)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 胃癌 / オルガノイド / 幹細胞

Outline of Final Research Achievements

Gastric cancer (GC) is generally sub-classified into "intestinal type" that expresses MUC2 or CD10 and "gastric type" that expresses MUC5AC or MUC6 based on the immunohistochemical analysis. It is well known that both intestinal and gastric type cancers are underpinned by different genetic and molecular background.
We generated a GC organoid library that is composed of 50 GC cases, including the results of several IHC staining, MSI and mutation status. We also examined the drug sensitivity against representative anti-cancer drugs.
We then performed RNA sequence using GC organoids with intestinal and gastric types, and found out several candidate genes that are involved in the resistance against 5-FU and oxaliplatin. Currently, several studies that aim to reveal molecular machinery concerning attainment of drug resistance are ongoing. We are also conducting a screening of the specific inhibitors against above-mentioned candidates in collaboration with a pharmatheutic company.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

オルガノイドは幹細胞を豊富に含んでおり、胃癌オルガノイドは癌幹細胞を豊富に含んでいると考えられることから、今回同定した候補遺伝子は癌幹細胞を標的とした治療につながる可能性が考えられる。
胃癌オルガノイドを用いた研究はこれまでになく、非常に新規性の高い研究であると考えられ、根治を目指した癌幹細胞を標的とした治療開発に加えて、胃型、腸型胃癌の病態形成のメカニズムなど、様々な新知見をもたらすものと期待される。