Does SLFN11 stratify medulloblastomas to determine the appropriate treatment intensity?

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20953
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Gunma University
• Principal Investigator: Nakata Satoshi 群馬大学, 医学部附属病院, 助教 (10817191)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 髄芽腫

Outline of Final Research Achievements

We have shown in medulloblastoma through comprehensive database analysis and analysis of new samples from multiple centers that 1) SLFN11 alone has prognostic value significantly exceeding 33 existing prognostic factors, and 2) its expression is particularly strong in a group of patients with good prognosis with activation of the WNT signaling pathway. In addition, experiments using patient-derived cell lines and orthotopic xenograft models showed that 3) forced expression or knockout of SLFN11 increases or decreases sensitivity to DNA-disrupting anticancer drugs, respectively, and 4) upregulation of SLFN11 by HDAC inhibitors increases sensitivity to DNA-disrupting anticancer drugs. upregulation of SLFN11 by HDAC inhibitors increases sensitivity to DNA-disrupting anticancer drugs.

Free Research Field

悪性脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は髄芽腫の実臨床において大きなインパクトがあるものと考えられる。SLFN11発現量は免疫染色で精度良く評価可能であり、今後は個々の髄芽腫症例で術後早期に化学療法の感受性を予測することができる。その上で、SLFN11陽性の化学療法感受例に対しては照射線量を減量し晩期合併症を軽減、SLFN11陰性の化学療法抵抗例に対してはHDAC阻害剤を併用することでDNA傷害型抗がん剤治療への感受性を回復させる、という新たな戦略をとることが可能となる。