Precision-guided SHH blockade (vismodegib) + HDAC inhibition (vorinostat) accompanies 9-year remission in relapsed SHH medulloblastoma

Vorinostat is an oral histone deacetylase (HDAC) inhibitor and vismodegib is an oral SMO inhibitor targeting the Sonic Hedgehog (SHH) pathway; together with curcumin (multi-target natural product with reported anti-survival/anti–cell-cycle signaling effects), they were selected by a molecular tumor board after tumor/normal WES and tumor RNA-seq on NMTRC009 (NCT02162732) for a 6-year-old with relapsed SHH, TP53–wild-type medulloblastoma. After upfront resection + intensive multi-agent chemotherapy + high-dose consolidation with autologous stem cell transplant, the patient relapsed 9 months later with intracranial and spinal disease and then received vorinostat + vismodegib + curcumin for 1.5 years plus craniospinal proton radiation during the first 6 months (palbociclib was recommended but not given); the patient achieved a radiographic complete response by ~1.7 years and remained in remission 9 years after treatment initiation (last imaging May 8, 2025). Toxicity was mainly mild thrombocytopenia (leading to vorinostat discontinuation) and premature growth plate closure attributed to vismodegib (the only Grade 3+ AE); notably, long-term survival here exceeds typical post-relapse long-term survival of ~10–30% reported across relapsed medulloblastoma series, underscoring how unusual a durable CR is in this setting.