髄膜腫—Precision medicineの可能性

The Potential of Personalized/Precision Medicine for Meningiomas

Point

・髄膜腫において本邦で承認されている治療薬は存在しないが，国内外では分子標的治療薬や免疫チェックポイント阻害薬を使用した治験が行われている．

・髄膜腫の包括的遺伝子解析が進み，従来知られていたNF2遺伝子変異以外にも，いくつかの特徴的な遺伝子変異が同定された．

・発見された遺伝子変異は多くがNF2変異と相互排他的に存在し，precision medicineの標的となる可能性がある．

　Meningiomas are one of the most common primary brain tumors. The majority of patients with meningiomas can undergo curative resection or remain asymptomatic for a lifetime, but a minority of them have tumors with cumbersome clinicopathological features causing life-threatening disease. Although several cytotoxic agents and hormonal therapies have been tried for refractory and unresectable meningiomas, there are no effective drugs available for meningiomas so far. In the last decade, due to the rapid progress in comprehensive genomic research for individual tumors, novel somatic and recurrent mutations were discovered in meningiomas. The discovered somatic mutations were mostly mutually exclusive with NF2 gene alterations, and importantly, several of these mutations, such as AKT1 and SMO, are potentially actionable mutations for precision/personalized medicine. In addition, immunotherapy is another attractive treatment option for refractory meningiomas due to the development of immune checkpoint inhibitors. Herein, we describe the possibility of precision medicine for meningiomas according to each molecular aberrancy and present the currently ongoing clinical trials including hormonal therapy, targeted kinase inhibitors, and immunotherapy.