2023 Fiscal Year Final Research Report

Development of minimally invasive treatment in head and neck cancer focused on PI3K/Akt/mTOR pathway

Research Project

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Project/Area Number	21K09585
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56050:Otorhinolaryngology-related
Research Institution	University of the Ryukyus
Principal Investigator	Suzuki Mikio 琉球大学, 医学(系)研究科(研究院), 教授 (00226557)
Co-Investigator(Kenkyū-buntansha)	池上太郎琉球大学, 医学(系)研究科(研究院), 助教 (00754409) 真栄田裕行琉球大学, 医学(系)研究科(研究院), 准教授 (40264501) 平川仁琉球大学, 病院, 講師 (50437993)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	head and neck cancer / mTOR inhibitor / Torin / PLD inhibitor
Outline of Final Research Achievements	For the development of less invasive treatments for head and neck cancer, an analysis focusing on the PI3K/Akt/mTOR pathway was conducted. Using rapalogs (mTOR inhibitors) temsirolimus and everolimus, which are clinically applied in other cancers, along with Torin-1, 2, and PLD inhibitors, the effects of each drug alone and in combination with rapalogs were analyzed. All drugs showed antitumor effects at high concentrations. However, when used at or below clinical doses, the antitumor effects diminished. Examination of various combinations revealed that the combination of everolimus and Torin-1 demonstrated antitumor effects at low concentrations. In vivo analysis using immunodeficient mice confirmed the antitumor effects of this low-concentration combination. This study contributes to the development of less invasive treatments with fewer side effects.
Free Research Field	Head and neck cancer
Academic Significance and Societal Importance of the Research Achievements	頭頸部は多くの感覚器を含んでおり、呼吸、嚥下、発声、容貌などの関連から、頭頸部癌治療には生命予後だけでなく、治療後のQuality of Survivalが重要である。頭頸部癌ではPI3K/Akt/mTOR経路活性化が腫瘍増殖に深く関連している。本研究ではラパログ（mTOR阻害薬）と別の作用点を持つmTOR阻害薬Torin-1、 2に着目し、ラパログ、PLD阻害薬のin vitro, in vivoの効果を解析した。本結果から、ラパログとTorinを組み合わせることにより、それぞれ単独で用いるよりも相乗効果を示すことが分かった。本成果は、より低侵襲で副作用の少ない治療へ結びつくものである。