PFA
Posterior Fossa A — the most aggressive pediatric ependymoma subgroup; H3K27me3 loss driven by EZHIP overexpression.
Standard of care, prognosis, and what's under investigation
Standard of care. Maximal safe surgical resection followed by focal radiation is the established backbone. Chemotherapy generally has limited utility in PFA. Children under 3 years old face a particularly hard tradeoff: radiation is the most effective adjuvant therapy but carries substantial neurocognitive toxicity at that age.
Prognosis. 5-year overall survival is approximately 60% in the published literature — the most aggressive of the major ependymoma subgroups. Recurrence is common and salvage options are limited.
What's being investigated here. Two computational hypotheses are active: (1) a hypoxic-core / wound-healing-rim niche that may be vulnerable to multi-target drugs, and (2) CDK4/6 inhibitor activity (Palbociclib, Abemaciclib) ranking near the top of our drug-prediction engine for PFA samples. Both remain pre-clinical.
Research Use Only — no entry below is clinical-grade evidence.
Active hypotheses, data status, and blockers
- Leading hypotheses. Hypoxia–wound niche coupling (pfa1-niche) and CDK4/6 activity (pfa-cdk46).
- Data status — strengths. PFA is the largest molecular subgroup in the atlas (the bulk of posterior-fossa samples). Bulk-RNA signal is strong enough to support cross-sample correlation and drug ranking.
- Data status — weaknesses. No spatial transcriptomics ingested yet; compartmental signals (tumor vs myeloid) are invisible at bulk resolution.
- Key blockers. Donson 2022 Visium ingest is the cheapest decisive next step for the niche hypothesis. The parser is written and unit-tested against the 10x format.
- Framework note. The developmental-origin mechanism story for PFA was refuted at hallmark pathway resolution (falsification). The empirical drug-ranking finding stands; the textbook explanation does not.