Diagnostic and therapeutic strategies targeting microRNAs and epigenome alterations in biliary tract and pancreatic cancer stem cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26290049
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Keio University
• Principal Investigator: Saito Yoshimasa 慶應義塾大学, 薬学部, 准教授 (90360114)
• Co-Investigator(Renkei-kenkyūsha): SATO Toshiro 慶應義塾大学, 医学部, 准教授 (70365245) ; KANAI Yae 慶應義塾大学, 医学部, 教授 (00260315) ; OOE Tomoyuki 慶應義塾大学, 薬学部, 准教授 (30624283)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 胆道がん / 膵臓がん / がん幹細胞 / オルガノイド培養 / マイクロRNA / エピゲノム / 個別化治療

Outline of Final Research Achievements

Cancer stem cells are resistant to conventional chemotherapies and responsible for cancer initiation, invasive growth, and metastasis formation. The aim of this study is to develop a novel therapeutic strategy targeting biliary tract and pancreatic cancer stem cells. The newly developed 3D culture system called “organoid culture” allows long-term expansion of LGR5 positive stem cells into budding cyst-like structures (organoids) with properties resembling those of the original tissues. To reach our goal, we established organoids derived from biliary tract cancers and pancreatic cancers. We analyzed gene mutation and gene expression and performed drug screening test using these cancer organoids. Here we demonstrated that low molecular compounds and tumor suppressor microRNAs including miR-34a are safe and effective therapeutic drug candidates against biliary tract and pancreatic cancers.

Free Research Field

薬物治療学、消化器病学、分子腫瘍学