Elucidation of molecular mechanisms of resistance to MAP kinase inhibitor in pancreatic cancer and establishment of novel therapeutic strategy targeting to the resistance

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06992
• 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: Oita University
• Principal Investigator: Moriyama Masatsugu 大分大学, 医学部, 教授 (90239707)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 膵癌 / MAPキナーゼ阻害薬 / 耐性機序

Outline of Final Research Achievements

It has been shown that an activated MAP kinase contributes to maintain the higher levels of cell growth potential and invasiveness in pancreatic cancer. Therefore, an inhibitor to the MAP kinase is expected to be a promising agent against the pancreatic cancer. However, to date, several clinical trials have failed to demonstrate the efficacy of MAP kinase inhibitor to the patients with pancreatic cancer. In this study, we showed that Clusterin, expressed in pancreatic cancer cells, was involved in the increased cell viability and the resistance to MAP kinase inhibitor. Furthermore, we exhibited the synergistic suppressive effects on cell growth by combination of the treatment with MAP kinase inhibitor and downregulation of Clusterin.

Free Research Field

分子病理学

Academic Significance and Societal Importance of the Research Achievements

膵癌は最も予後不良な癌のひとつである。その理由として、顕著な有効性を示す抗がん剤治療法が開発されていないことが挙げられる。したがって膵癌の治療成績を改善するためには、膵癌の発症・進展に関わる分子メカニズムを解明して、その知見に基づく新規治療法の開発が強く望まれる。
本研究では、MAPキナーゼ阻害薬抵抗性獲得に関与する分子Clusterinを同定した。さらに、Clusterinを標的とした治療を併用することでMAPキナーゼ阻害薬の有効性が回復することを示した。今後、ClusterinとMAPキナーゼを標的とする新規膵癌治療法の確立を目指す。