Development of novel gene therapy for head and neck cancer applying demethylation mechanism

• Project/Area Number: 17K11403
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Jichi Medical University
• Principal Investigator: Kanazawa Takeharu 自治医科大学, 医学部, 教授 (20336374)
• Co-Investigator(Kenkyū-buntansha): 今吉 正一郎 自治医科大学, 医学部, 助教 (00570186) ; 水上 浩明 自治医科大学, 医学部, 教授 (20311938) ; 草鹿 元 自治医科大学, 医学部, 教授 (00265258)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 頭頸部癌 / 唾液腺導管癌 / DNAメチル化 / エピジェネティックス / 遺伝子導入 / 癌抑制遺伝子 / メチル化

Outline of Final Research Achievements

Head and neck squamous cell carcinoma (NHSCC): Significant methylation of the TET family was observed in the cell lines. In addition, its methylation significantly suppressed the survival time in HNSCC patients. We also reconfirmed the function of GALR, which is strongly associated with the TET family, and confirmed the methylation of the TET family in GALR-transduced cell lines. Salivary duct carcinoma (SDC): The methylation rates of GALR1 and GALR2 in SDC were significantly increased compared to normal tissue and significantly correlated with decreased survival. In addition, DNA methylation of TET2 and TET2 was significantly higher than that of normal tissues. Examination of external database: Hypermethylation of GAL / GALR2 significantly suppressed the survival time of HNSCC.

Academic Significance and Societal Importance of the Research Achievements

頭頸部癌治療では新たな治療法の開発が望まれている．DNAメチル化は，エピジェネティックスとして知られる普遍的な遺伝子制御機構の１つであり，癌抑制遺伝子はDNAメチル化によりその機能を抑制されている． TET familyは，DNA脱メチル化を促進する因子でありTET2 family と関連する癌抑制遺伝子のDNAメチル化が今後の頭頸部癌診療において重要な意味を持つことが予想される．このため，頭頸部癌でのこれらのDNAメチル化およびDNA脱メチル化機構を解明することは新規遺伝子治療薬の開発を促進および既知の頭頸部癌化学療法の進歩に大きく寄与するものと考えられる．

Research Products

• [Journal Article] Promoter methylation of galanin receptors as epigenetic biomarkers for head and neck squamous cell carcinomas (2019)
  • Author(s): Kanazawa Takeharu、Misawa Kiyoshi、Shinmura Kazuya、Misawa Yuki、Kusaka Gen、Maruta Mikiko、Sasaki Toru、Watanabe Yusuke、Carey Thomas E.
  • Journal Title: Expert Review of Molecular Diagnostics Volume: 19 Issue: 2 Pages: 137-148
  • DOI: 10.1080/14737159.2019.1567334
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic inactivation of galanin receptors in salivary duct carcinoma of the parotid gland: Potential utility as biomarkers for prognosis (2018)
  • Author(s): Kanazawa Takeharu、Misawa Kiyoshi、Fukushima Hirofumi、Misawa Yuki、Sato Yukiko、Maruta Mikiko、Imayoshi Shoichiro、Kusaka Gen、Kawabata Kazuyoshi、Mineta Hiroyuki、Carey Thomas、Nishino Hiroshi
  • Journal Title: Oncology Letters Volume: 15 Pages: 904-9050
  • DOI: 10.3892/ol.2018.8525
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] DNA methylation in Thyroid Cancer (2017)
  • Author(s): Kanazawa T, Kisawa K.
  • Organizer: 2nd Congress of Asia-Pacific Society of Thyroid Surgery.
  • Int'l Joint Research