Exploration of metabolic factors to inhibit tumor-specific p53 gene therapy in pancreatic cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07219
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Okayama University
• Principal Investigator: TAZAWA HIROSHI 岡山大学, 大学病院, 准教授 (90415513)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膵臓癌 / 代謝サブタイプ / 解糖系代謝 / p53 / アデノウイルス / ミトコンドリア / 個別化医療

Outline of Final Research Achievements

Genomic medicine based on gene mutations is expected to provide precision medicine in cancer patients. However, genomic medicine against KRAS/p53-mutant pancreatic cancer remains to be developed. Here, we show that glycolytic pancreatic cancer cells were sensitive to tumor-specific replication-competent p53-inducing oncolytic adenovirus OBP-702. Moreover, combination of mitochondrial metabolism inhibitor promoted virus sensitivity in non-glycolytic pancreatic cancer cells by inducing glycolysis. Mitochondrial metabolism may be therapeutic target to improve resistance to virotherapy. Thus, the development of biomarker to evaluate glycolysis in pancreatic cancer is important for precision virotherapy.

Free Research Field

分子腫瘍学、遺伝子治療学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、解糖系代謝が亢進した膵臓癌に対して癌特異的に制限増殖するp53誘導性アデノウイルスOBP-702を用いたp53遺伝子治療が抗腫瘍効果を発揮することを明らかにした。さらに、代謝調節剤を併用して解糖系代謝を誘導することでウイルスへの抵抗性を改善できる可能性も示した。膵臓癌に対する個別化治療の開発は膵臓癌患者の生命予後の改善につながることが期待される。