Towards establishment of combination therapy according to molecular profiling for atypical/anaplastic meningiomas

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09464
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Keio University
• Principal Investigator: Yohida Kazunari 慶應義塾大学, 医学部(信濃町), 名誉教授 (70166940)
• Co-Investigator(Kenkyū-buntansha): 佐々木 光 慶應義塾大学, 医学部(信濃町), 講師 (70245512)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 悪性髄膜腫 / 異型髄膜腫 / 遺伝子発現プロファイル / がん遺伝子パネル検査 / 異種移植 / 幹細胞 / 培養

Outline of Final Research Achievements

More than 20 atypical/anaplastic meningiomas and 8 grade 1 meningiomas without evidence of recurrence for more than 5 years were analyzed for expression profiling and mutation profiling (cancer gene panel test) with the aim to classify atypical/anaplastic meningiomas according to molecular pathway correlated with patient prognoses. Preliminary results showed that atypical/anaplastic meningiomas were classified into 3 groups by hierarchical clustering based on expression profiling. In addition, we have established a malignant meningioma cell line and its xenograft in mice that apparently has stem cell property. Efficacy assays are being performed by mono- or combination therapy with molecular targeted drugs according to mutation profiles in 2 malignant meningioma cell lines; the above mentioned one established by ourselves and a commercial one, with the aim to develop the most efficacious drug combination in each of the molecular groups of atypical/anaplastic meningiomas.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

WHO分類Grade 2/3の異形性・退形成性髄膜腫（悪性髄膜腫, 国内で約500人/年発生）は、手術および放射線治療を行っても高率に局所再発あるいは頭蓋内・外転移を繰り返す、最も治療困難な脳腫瘍のひとつであり、有効な新規治療法を開発することが急務である。現状では、たとえ保険診療がん遺伝子パネル検査で治療標的となる遺伝子異常が発見されても、施行可能な治療は、NCCH1901試験等への参加による分子標的薬単剤治療である。悪性化メカニズムによる悪性髄膜腫の分類、そしてその各群に対する適切な治療薬の組み合わせが確立されれば、先進医療などの枠組みにより、新たな治療法が提供できる可能性がある。