Can B2 Adrenergic-Neurotrophin Feedforward Loop Promote Biliary Tract Cancer (BTC) and be the therapeutic target for BTC ?

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K21275
• Project/Area Number (Other): 18H06166 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0901:Oncology and related fields
• Research Institution: Nagasaki University
• Principal Investigator: TANAKA Takayuki 長崎大学, 病院(医学系), 助教 (40823290)
• Project Period (FY): 2018-08-24 – 2021-03-31
• Keywords: 肝内胆管癌 / 交感神経刺激 / 神経微小環境 / アドレナリン受容体2（ADRB2） / 神経成長因子（NGF）

Outline of Final Research Achievements

Intrahepatic cholangiocarcinoma is a malignant disease with an extremely poor prognosis. Since the mechanism of the disease remains still unknown, effective treatment and prevention methods have not been established. Following the report that sympathetic stress-induced catecholamines and adrenergic receptor2 (ADRB2), are involved in pancreatic cancer, our study realized that the same mechanism as pancreatic cancer exists in biliary carcinogenesis and cancer promotion, and that ADRB2-mediated mechanisms exist in the neural microenvironment of intrahepatic cholangiocarcinoma. This finding suggested that the neuronal microenvironment in intrahepatic cholangiocarcinoma may be mediated by ADRB2, which may become a target for the treatment of cholangiocarcinoma with poor prognosis.

Free Research Field

肝胆膵・移植外科

Academic Significance and Societal Importance of the Research Achievements

肝内胆管癌は５年生存率30％と予後不良な疾患であり、胆管癌も膵癌同様、前癌病変からの多段階発癌を特徴としている。また、同じ交感神経支配下にある肝内胆管癌も同様のメカニズムが存在している可能性が非常に高い。本研究では交感神経（ストレス）が誘発するカテコラミンとその受容体であるADRB2の陽性率が高いほど予後不良であり、またそのADRB2-カテコラミン伝達は肝内胆管癌治療の標的になる可能性が示唆された。それゆえに、今後の肝内胆管癌の治療に飛躍的な効果を生み出すことが期待できる。