Do CDK4/6 inhibitors concentrate in PFA ependymoma?
PFA radial-glia CDK4/6 → Abemaciclib
Do CDK4/6 inhibitors concentrate in PFA samples (n=124, broad) relative to PF-B (n=4), PF_SE (n=7), and other EPN (n=235)?
✓ Hypothesis supported
At least one CDK4/6 inhibitor passes the PFA-specificity gate (top-5 in ≥40% of PFA with median rank ≤ 15). PNOC/COG abemaciclib retrospective re-analysis is justified.
CDK4/6 inhibitor head-to-head
Named drugs checked against the gate (top-5 in ≥40% of PFA AND median rank ≤ 15).
| Drug | PFA top-5 | PFA median rank | Other-EPN top-5 | Other-EPN median rank | Top drivers (PFA) | Gate |
|---|---|---|---|---|---|---|
| Abemaciclibcalibrated (0%) | 37.1% | 13 | 30.6% | 56 | GSK3B,GSK3A,CAMK2A,PIM1,EGFR | ✗ fail |
| Palbociclibcalibrated (0%) | 56.5% | 2 | 36.6% | 70 | DYRK1B,PLK1,GSK3B,CAMK2A,EIF2AK2 | ✓ pass |
| Ribociclibcalibrated (0%) | 0.8% | 35 | 1.3% | 49 | LYN,EGFR,GSK3A,CAMK2B,CAMK2D | ✗ fail |
What the ranker picks for PFA — top 25 drugs by top-5 frequency
| Drug | PFA top-5 | PFA median rank | Other-EPN top-5 | Primary drivers | CDK4/6? |
|---|---|---|---|---|---|
| Encorafenibcalibrated (0%) | 58.9% | 4 | 32.8% | GSK3B,GSK3A,NLK,LYN,RAF1 | |
| Palbociclibcalibrated (0%) | 56.5% | 2 | 36.6% | DYRK1B,PLK1,GSK3B,CAMK2A,EIF2AK2 | ✓ |
| Abemaciclibcalibrated (0%) | 37.1% | 13 | 30.6% | GSK3B,GSK3A,CAMK2A,PIM1,EGFR | ✓ |
| Tofacitinibcalibrated (0%) | 26.6% | 69 | 30.6% | JAK2,JAK1,TYK2,LYN,EGFR | |
| Zanubrutinibcalibrated (0%) | 24.2% | 84 | 33.2% | EGFR,LCK,LYN,FYN,CSK | |
| Darovasertibcalibrated (0%) | 21.8% | 12 | 7.7% | GSK3B,NLK,GSK3A,LYN,PIM1 | |
| Gedatolisibcalibrated (0%) | 18.5% | 14 | 6.8% | GSK3B,EGFR,FYN,LCK,PRKX | |
| Tucatinibcalibrated (0%) | 18.5% | 59 | 18.3% | JAK1,JAK2,LYN,GSK3B,LCK | |
| Rabusertibcalibrated (0%) | 18.5% | 29 | 26.4% | CAMK2A,CAMK2D,GSK3B,LYN,RAF1 | |
| Temsirolimuscalibrated (0%) | 15.3% | 27 | 9.4% | EGFR,GSK3B,GSK3A,ABL1,WEE1 | |
| Mobocertinibcalibrated (0%) | 14.5% | 54 | 15.7% | EGFR,LYN,ABL1,GSK3B,FYN | |
| Defactinibcalibrated (0%) | 13.7% | 35 | 4.7% | GSK3B,EGFR,LCK,JAK2,PLK1 | |
| Tepotinibcalibrated (0%) | 13.7% | 22 | 3.4% | GSK3B,LYN,ABL1,LCK,AXL | |
| Sirolimuscalibrated (0%) | 12.1% | 23 | 6.4% | EGFR,GSK3B,GSK3A,ABL1,AKT1 | |
| Ibrutinibcalibrated (0%) | 12.1% | 81 | 16.6% | LYN,EGFR,FYN,LCK,CSK | |
| Deucravacitinibcalibrated (0%) | 12.1% | 23 | 2.6% | GSK3B,LYN,ABL1,LCK,FGFR1 | |
| Duvelisibcalibrated (0%) | 11.3% | 22 | 3.8% | LYN,GSK3A,ABL1,EGFR,AKT1 | |
| Entrectinibcalibrated (0%) | 11.3% | 82 | 17.4% | LYN,FYN,LCK,ABL1,JAK2 | |
| Umbralisibcalibrated (0%) | 9.7% | 64 | 11.5% | LYN,LCK,JAK2,JAK1,ABL1 | |
| Futibatinibcalibrated (0%) | 8.9% | 51 | 8.9% | JAK2,FGR,JAK1,FGFR1,RET | |
| Netarsudilcalibrated (0%) | 8.9% | 26 | 15.3% | AKT1,PRKX,ROCK1,AKT3,LRRK2 | |
| Alpelisibcalibrated (0%) | 8.9% | 58 | 8.5% | EGFR,JAK2,JAK1,ABL1,GSK3B | |
| Quizartinibcalibrated (100%) | 8.1% | 30 | 17.4% | GSK3B,FYN,PDGFRB,RET,FLT3 | |
| Asciminibcalibrated (0%) | 7.3% | 14 | 7.2% | GSK3B,ABL1,AKT1,LYN,JAK2 | |
| Everolimuscalibrated (0%) | 5.6% | 26 | 5.1% | EGFR,GSK3A,ABL1,AKT1,WEE1 |
How this test runs (caveats)
Radial-glia signature (HES1/FABP7/SLC1A3/PAX3/ZIC1/MKI67/CDK6) from raw RNA is the PRD's preferred input. Raw RNA isn't in the precompute pipeline; this test uses F-40 selectivity-adjusted rank for CDK4/6 inhibitors against the full KIRhub panel as the subgroup-specificity proxy. CDK6/CDK9 in primary_driver_kinases is the gene-level signal we CAN detect.
PFA-broad cohort = EPN_classification = PF-A OR EPN_subtype = "Posterior Fossa EPN" without PF-B/PF_SE marker. The explicit PF-A count is 17; with the broad definition we get n=124. Further ingestion of Pajtler 2015 would expand explicit PF-A to ~200.
# Platform Saifudeen, A., et al. (2026). KIRhub: a falsification-first research workbench for translational oncology. Nature Biotechnology. https://doi.org/10.1038/s41587-026-03090-8 # Data source McFerrin, L. G., et al. (2018). Oncoscape: a tool for interactive cancer genomics data analysis. Nature Genetics. Arora, S., et al. (2026). A pan-pediatric brain tumor reference map: medulloblastoma and ependymoma in shared UMAP space. Neuro-Oncology. # Datasets used in this insight Oncoscape pediatric brain tumor compendium (n=1,358) # Provenance insight_id: pfa-cdk46