Therapeutic development targeting ATP-related cancer metabolism using the PDX model of malignant pleural mesothelioma

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18217
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Hiroshima University (2021-2022); Department of Clinical Research, National Hospital Organization Kure Medical Center (2020); Higashihiroshima Medical Center (2019)
• Principal Investigator: Kamigaichi Atsushi 広島大学, 病院(医), 医科診療医 (70825231)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: がん代謝 / 悪性胸膜中皮腫

Outline of Final Research Achievements

First, we focused on lung adenocarcinoma, for which specimens are relatively easily obtained, and classified them into Glycolysis and Oxphos types as ATP-related cancer metabolism. The classification has demonstrated Oxyphos phenotype of lung. The inhibitors targeting mitochondrial respiration markedly suppressed cell proliferation in lung adenocarcinoma cell lines at low concentrations compared with normal cells.
Next, the metabolic types classification of malignant pleural mesothelioma was conducted using TCGA database. When gene expression of ATP-related cancer metabolism of MPM was compared to normal tissue, the difference of them tended to be more in biphasic and sarcomatoid type MPM than in epithelial type MPM. Among these genes, gene “X” related to glycolytic metabolism of MPM was identified. We further plan to pursue the development of therapies targeting this candidate gene.

Free Research Field

肺癌、悪性胸膜中皮腫

Academic Significance and Societal Importance of the Research Achievements

悪性胸膜中皮腫は希少がんではあるが、その予後は非常に不良であり、現状の治療法では十分とは言えず新たな治療法の開発が望まれている。近年、免疫チェックポイント阻害薬が注目されているが、有効例は限られており、次を見据えた治療開発は必須である。がん特異的優位代謝別に治療法が選択できれば、難治性かつ治療選択肢の少ない悪性胸膜中皮腫の患者が受ける恩恵は計り知れない。本研究では肺腺癌において、がん代謝を標的とした阻害薬で細胞増殖抑制効果が認められることが示唆され、悪性胸膜中皮腫検体にて解糖系代謝に関わる遺伝子を同定できた。今後、これを標的として、がん代謝別の治療法を確立することが期待される。