Development of novel therapeutic strategies for refractory oral cancer targeting higher-order epigenomic regulation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09727
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kumamoto University
• Principal Investigator: Hirosue Akiyuki 熊本大学, 病院, 助教 (00638182)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 口腔癌 / 治療抵抗性 / エピゲノム / ヒストン修飾 / BRD4

Outline of Final Research Achievements

The morbidity of oral squamous cell carcinoma (OSCC) is increasing with the aging of the population. High malignant potential such as metastasis and therapeutic resistance is a major factor that reduce survival. Therefore, to develop the novel diagnostic and therapeutic methods based on epigenome profiles, we investigated the higher-order epigemomic alterations related treatment resistance in OSCC. It was revealed that BRD4 contributes to metastatic potential in OSCC through the higher-order epigenomic regulation of the MMP2 gene. It was also indicated that IGFBP-3 is involved in radioresistance of OSCC by promoting DNA repair. These findings suggest that an approach targeting epigenome regulation may be a novel therapeutic strategy for refractory oral cancer.

Free Research Field

口腔癌

Academic Significance and Societal Importance of the Research Achievements

口腔扁平上皮癌(OSCC)の治療抵抗性に関して高次エピゲノムの制御に着目した研究はほとんどない。そのため、OSCCの転移や放射線耐性に関連する分子メカニズムをエピゲノム制御の観点から解明した本研究は難治性口腔癌の新規の治療戦略に繋がる可能性もあり学術的意義が大きい。また、本研究は現在注目を浴びているがんの個別化治療やPrecision Medicine(精密医療)の発展に貢献できる可能性もあり、さらに幅広い生命現象へ関与している高次エピゲノムの制御機構の解明は、様々な疾患の診断や治療に貢献できる可能性もあり社会的意義も大きい。