Development of novel therapy of osteosarcoma targeting the post-transcriptional modification

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16325
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kato Shota 東京大学, 医学部附属病院, 助教 (70868257)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 骨肉腫 / 糖鎖修飾 / 発現解析

Outline of Final Research Achievements

We conducted the planned experiments to elucidate how post-translational protein glycosylation occurring in osteosarcoma cells is involved in tumor cell survival and proliferation and to examine whether its inhibition could be a new therapeutic target. Comprehensive measurements were made on changes in phosphorylated signaling proteins that occur before and after the knockdown of candidate genes and changes in gene expression status. In addition, candidate gene knockdown experiments were performed on tumors generated in vivo in immunosuppressed mice. These studies have elucidated the critical role of the candidate gene in tumor growth and demonstrated that the gene is a promising therapeutic target.

Free Research Field

小児がん

Academic Significance and Societal Importance of the Research Achievements

骨肉腫の治療成績は長きに渡り向上が乏しく、新規治療開発による予後の向上が強く求められる疾患である。各種の癌腫において遺伝子変異を標的とした新規治療が開発されているが、骨肉腫においてはそのようなアプローチは取りづらいという問題点があった。本研究は発現解析をもとに抽出した新規治療標的遺伝子に対して、その機能解析と治療標的としての評価を行ったものである。今後の併用薬の選出および動物実験の進行により、将来的には骨肉腫の新規治療法の創出に結びつけることを期待できる。