Patient: 7-year-old male with glioblastoma multiforme (WHO Grade IV) post–partial resection and chemoradiotherapy
Clinical Testing:
Alterations: TP53, CDKN2A, LATS1, ATM, BRCA2, RAD50, MSH2, MLH1, PMS2, XPC, EGFR, NF1, PIK3CA, PTEN, NPRL2, ATRX, SETD2
Genes: DDR, PI3K/mTOR, RAS/MAPK, and cell-cycle pathway genes
Treatment Options: PARP inhibitors (HRR/MMR defects), immunotherapy (PD-L1, MMR), PI3K/mTOR inhibitors, MEK inhibitors (NF1), and CDK4/6 inhibitors, with clinical-trial–based targeted combinations.
Indication: Pediatric glioblastoma with residual tumor and progression despite standard therapy.
Research Findings: Multi-omic profiling identified widespread DNA repair, PI3K/mTOR, and MAPK pathway disruptions, revealing targetable vulnerabilities. HRR/MMR defects support PARP inhibitors and immunotherapy, while NF1 and PIK3CA/PTEN alterations suggest pathway-specific targeted options.