Yi et al. (82) described a case of glioblastoma with secondary OS in which exome sequencing-guided therapy—combining EVR, tumor-treating fields (TTFields), pembrolizumab, and temozolomide—achieved exceptional benefit through dual mechanisms: (1) targeting PTEN loss in glioblastoma to suppress mTORC1-driven proliferation and enhance temozolomide chemosensitivity; and (2) exploiting MSH3/ERCC4 mutation-associated DNA repair defects in secondary OS by disrupting mTOR signaling. This evidence concerns the gene MSH3 and glioblastoma.