Developing therapies that target splicing abnormalities that make squamous cell carcinoma of the head and neck highly malignant.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16831
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Osaka University
• Principal Investigator: Kitamura Koji 大阪大学, 大学院医学系研究科, 招へい教員 (40804365)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 頭頸部扁平上皮癌 / RNAスプライシング / 核酸医薬

Outline of Final Research Achievements

Using PAR-CLIP (photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation), we identified the binding sequence of SF3B2 specific for head and neck squamous cell carcinoma (HNSCC). Decoys with the sequence were generated and introduced into HNSCC cell lines. However, cell death was observed in both control and decoys with the specific sequence in the transfected cell lines. The result was attributed to cytotoxicity of the modifier due to the instability of the decoys. Further modification conditions were investigated, but the situation did not improve and it was technically difficult to develop a decoy-based therapy at this time.

Free Research Field

頭頸部癌

Academic Significance and Societal Importance of the Research Achievements

核酸医薬によるスプライシング制御の治療法が開発されれば、従来の低分子医薬や抗体医薬とは異なり、癌の高悪性化に関わる選択的スプライシング異常をRNAのレベルで特異的に制御できるため、新たなアプローチで、特異性が高く、また副作用が少ない新たな治療法への発展が期待できる。本研究ではSF3B2の結合配列は同定できており安全で腫瘍への送達が可能な核酸医薬が開発されれば治療法として急速に普及することが予想されることから、その一歩として意義ある研究であると考える。