Development of novel treatment targeting mTOR pathway Raptor in HPV-related head and neck cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18318
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: University of the Ryukyus
• Principal Investigator: Uehara Takayuki 琉球大学, 医学部, 委託非常勤講師 (00644402)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: HPV関連頭頸部癌 / Raptor / PI3K/Akt/ｍTOR経路

Outline of Final Research Achievements

We have shown in previous studies that Raptor, a component of mTORC1, is an important target factor in the PI3K/Akt/mTOR pathway associated with cell proliferation for HPV-associated head and neck cancer. In this study, we investigated the efficacy of mTOR and Raptor targeting mTOR and using mTOR inhibitors (temsirolimus, Torin2) against Raptor high-expressing HPV16-associated cancer cell UMSCC047 and Raptor low-expressing HPV-unrelated cancer cell SAS strains. In the WST-1 study, a synergistic growth inhibitor effect was observed in HPV-related cell lines compared to unrelated strains, with the combination of the mTOR inhibitors described above. Currently, we are investigating the effects of the drug in a subcutaneous transplantation model in immunodeficient mice.

Free Research Field

頭頸部癌

Academic Significance and Societal Importance of the Research Achievements

HPV関連頭頸部癌は本邦でも近年増加傾向にあり、その治療選択肢の拡大、特に創薬開発や従来薬における適応拡大が見込まれることは社会的に意義が高い。今回の我々の検討では分子標的治療の分野で新たな治療ターゲット候補についてその有効性を、まずは基礎実験で細胞株および動物実験において解析し、将来的に臨床での応用を目指すことを目的とする。Raptorを標的とした治療においては新薬創薬をmTOR経路の阻害剤については従来薬を利用した治療への応用が期待できると考える。