Study on a novel mechanism of gemcitabine resistance

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15648
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Nara Medical University
• Principal Investigator: Fujiwara-Tani Rina 奈良県立医科大学, 医学部, 助教 (20783872)
• Research Collaborator: KUNIYASU Hiroki
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 膵管癌 / ゲムシタビン / 薬剤耐性 / MAST4 / AKT / 酸化ストレス

Outline of Final Research Achievements

In the gemcitabine resistant strain MIA-PaCa2-GEM, MAST4 expression was enhanced compared to the parent strain MIA-PaCa2. MAST4 expression has been correlated with cancer progression, poor prognosis, and gemcitabine resistance in human pancreatic ductal carcinoma. When MAST4 was knocked down in MIA-PaCa2-GEM, gemcitabine resistance disappeared. MAST4 interacts with AKT3 in the nucleus, and it is thought that AKT3 activation induces gemcitabine resistance via the AKT3-target genes, such as FoxO3. Moreover, it was thought that MAST4 upregulation was induced by miR 582-5p downregulation. MAST4 is a novel gemcitabine resistance gene in pancreatic ductal cancer and a prognostic factor, and is expected as a novel molecular target in pancreatic ductal cancer.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

膵管癌は、早期診断・早期治療が困難で生物学的悪性度も高く、最も悪性度の高い難治癌である。治療困難の要因の一つが有効な抗がん剤の少なさと耐性獲得による抗がん剤の無力化である。ゲムシタビンは膵管癌に有効性な数少ない抗がん剤の一つであるが、多くの症例では投与中に耐性を生じ効果が失われる。本研究ではゲムシタビン耐性を解除する新たな分子標的を見出すことに成功しており膵管癌の治療の改善につながると期待される。