DKK2 targeting therapy for cholangiocarcinoma found by exhausted gene analysis.

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18124
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: NAKAGAWA Shigeki 熊本大学, 病院, 非常勤診療医師 (10594872)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 胆管癌 / DKK2 / 細胞周期 / 抗癌剤 / 腫瘍免疫

Outline of Final Research Achievements

Surgery is the only treatment for the cure of cholangiocarcinoma, but the prognosis after surgery is still poor. We search the new therapeutic target from the exhaustive analysis of cholangiocarcinoma gene expression database. We found the DDK2 was strongly associated with poor prognosis of cholangiocarcinoma patients and clarify the mechanism haw DKK2 works in cholangiocarcinoma. DDK2 inactivate the CD8 positive T cells by blocking the WNT signal, and help the cancer cells gain the immune tolerance.

Free Research Field

消化器外科、肝胆膵外科、胆道癌、バイオインフォマティクス

Academic Significance and Societal Importance of the Research Achievements

今回の研究において、抗がん剤の選択肢の少ない胆管癌において治療の標的となる遺伝子、DKK2を発見した。更にその遺伝子の、胆管癌における働きを明らかにしたところ、免疫細胞のWNTシグナルという細胞増殖シグナルを抑えて腫瘍免疫を抑制することで、癌細胞を活性化している事が明らかとなった。今後研究を重ね、抗がん剤として実用化される事が期待される。