Development of novel therapeutic strategies for intractable pediatric cancers based on the multi-omics information

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04224
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto University (2018-2019); The University of Tokyo (2017)
• Principal Investigator: Takita Junko 京都大学, 医学研究科, 教授 (00359621)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 小児がん / 発現プロファイル / 治療標的 / 神経芽腫 / 横紋筋肉腫 / 骨肉腫

Outline of Final Research Achievements

To explore therapeutic gene targets in intractable pediatric cancers, we conducted multi-omics analysis in a large number of clinical samples. Based on the evolutional analyses, we found that NOTCH1 is an important driver in the development and progression of pediatric T cell acute lymphoblastic leukemia. In addition, the multi-omics information of 90 neuroblastoma cases including recurrent or metastatic tumors deposited in open database (TARGET) provided that PHGDH would be a promising therapeutic target in untreatable neuroblastoma cases. Our large-scale data analysis revealed that C1GALT1 is a candidate gene target in osteosarcoma, and also showed that FGFR4 inhibition could be a promising therapy for rhabdomyosarcoma.

Free Research Field

小児がん

Academic Significance and Societal Importance of the Research Achievements

本研究では、多層的オミックス解析を駆使して、難治性小児がんの治療標的の探索を行い、小児T細胞性急性リンパ性白血病におけるNOTCH1が難治性に寄与することを見出し、また新たな治療標的として、神経芽腫におけるPHGDH、骨肉腫におけるCIGALT1を同定した。さらにFGFR4の阻害が横紋筋肉腫に治療に有効となりうることを見出した。本研究の成果により、難治性小児がんの新たな治療スキームを提案し、治療の最適化を実現することは、小児がんの予後の改善ならびにQOLの向上に多大な貢献をなすものと考えられる。