脳腫瘍におけるがんゲノム医療の現在と未来

Cancer Genomic Medicine in Neuro-Oncology Practice

Point

・がん遺伝子パネル検査は，脳腫瘍領域において治療標的となる遺伝子異常を網羅的に検出し個別化医療を実現する．

・エキスパートパネルとがんゲノム情報管理センターを活用したがんゲノム医療により，標的治療や治験における治療機会が提供される．

・IDH，BRAF，NTRK，TMB-Highを標的とした治療が実用化され，脳腫瘍診療の新たな選択肢となっている．

　Cancer genomic medicine is an integral component of neuro-oncology, enabling personalized treatments based on tumor-specific genomic alterations. In Japan, comprehensive genomic profiling (CGP) is performed using several tissue- and plasma-based platforms to detect genomic mutations, copy number alterations, gene fusions, tumor mutational burden, and other molecular biomarkers. Tissue-based assays are preferred for brain tumors because of the limited sensitivity of plasma testing. CGP results were interpreted by expert molecular tumor boards supported by the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), integrating genomic and clinical data and providing information on potential targeted therapies and clinical trials. Real-world studies have demonstrated that actionable alterations can be identified in most patients, although only a few patients ultimately receive genomically matched treatments. However, the selected patients may achieve meaningful clinical benefits. Currently, approved molecularly targeted therapies in neuro-oncology include vorasidenib, dabrafenib plus trametinib, entrectinib or larotrectinib, and pembrolizumab for IDH1/2-mutant gliomas, BRAF V600E-mutant gliomas, NTRK fusion-positive tumors, and TMB-high tumors, respectively. Future challenges include improving patient access to genomic medicine, optimizing the timing of testing, expanding genomic analyses, and facilitating the development of novel targeted therapies for rare brain tumors.