Exploring novel therapeutic targets for malignant mesothelioma using synthetic lethality.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20854
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Mukai Satomi 愛知県がんセンター(研究所), 分子腫瘍学分野, 研究員 (10706146)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 悪性中皮腫 / NF2

Outline of Final Research Achievements

Malignant mesothelioma is a rare, refractory cancer with a poor prognosis and a five-year survival rate of less than 10%. Many of the high frequency of genetic mutations identified in malignant mesothelioma are cancer-suppressor genes, which has delayed the development of molecular targeted drugs. Recently, anti-cancer drug development by synthetic lethal gene screening has been conducted for various cancers, but malignant mesothelioma has lagged behind in research due to the paucity of available samples. In this study, we attempted to identify the NF2 synthetic lethal gene, which is frequently mutated in malignant mesothelioma, by CRISPR library screening using more than 30 cell lines originally established from Japanese malignant mesothelioma patients.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

これまで、NF2 が欠損した悪性中皮腫における腫瘍進展機構として、腫瘍抑制シグナル伝達経路である Hippo 経路の破綻が原因であると報告されてきたが、本研究においては、Hippo 経路の寄与は小さいものが多く、その他のシグナル伝達経路が原因である可能性が高いことが明らかとなった。本研究によって明らかとなる合成致死遺伝子を標的とする薬剤が、NF2 欠損悪性中皮腫患者に対する新規の分子標的薬として期待される。