Development of novel multidisciplinary therapeutic strategies by regulating the expression of pancreatic cancer resistance-associated molecules.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16430
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Nara Medical University
• Principal Investigator: Nagai Minako 奈良県立医科大学, 医学部, 学内講師 (80646092)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 治療抵抗性関連遺伝子 / CD200 / 治療抵抗性膵癌

Outline of Final Research Achievements

The plan was to identify genetic mutations characteristic of treatment-resistant acquired pancreatic cancer and to comprehensively elucidate the association between the identified candidate genes and CD200 expression, the mechanism of treatment resistance and the anti-tumour effect of complementary gene knockdown. In a tumour immunology study, the association with peri-neoplastic infiltrating lymphocytes showed that IL-2 was significantly reduced in CD200-expressing patients, indicating the possibility of treatment resistance. In order to identify genes associated with treatment resistance, genetic analysis was performed by classifying cases that were resistant to treatment and those that responded to treatment. However, it was not possible to identify or detect specific genes that were associated with treatment resistance.

Free Research Field

膵癌

Academic Significance and Societal Importance of the Research Achievements

難治性膵癌において，抗癌剤や放射線などに対する集学的治療が奏効しない遺伝子変異を同定することができ，それに対する対策を取ることができれば，根治が困難とされる膵癌においても長期生存あるいは根治の可能性が得られる可能性が広がると考えれれる．治療抵抗性を示す遺伝子を有する膵癌に対して有効な膵癌治療薬を開発のため治療抵抗性遺伝子の同定を進めてきたが．免疫不活化分子として知られているCD200の発現が膵癌治療抵抗に大きく関わっていることはわかったが，治療抵抗性に特徴的な遺伝子の同定まで至らず，今後さらに検討を進めて行くことで個別化治療の確立に役立つと思われる．