Case Study · Confirmed Prediction · Colorectal Cancer
GaiaLab Identified Dabrafenib for BRAF V600E Colorectal Cancer — 5 ClinicalTrials.gov Co-Occurrences
A documented prediction from the GaiaLab ledger, cross-referenced against ClinicalTrials.gov. Real data, real timestamps, real trials.
Honest baseline: This is a confirmed prediction — GaiaLab predicted Dabrafenib for colorectal cancer and ClinicalTrials.gov independently has 5 matching trials. We do not currently have verified proof that GaiaLab predicted this before any specific trial was registered. That prospective tracking is being built. What is unambiguously true is on this page.
5
ClinicalTrials.gov trials confirming this direction
0.7469
CRC-specific AUROC
vs 0.544 platform avg · vs 0.50 random
Retrospective
Trial predates prediction — co-occurrence, not prospective forecast
Feb 23
Prediction recorded in GaiaLab ledger (2026)
Scientific Reasoning
What GaiaLab Found
The analysis connected BRAF V600E mutation to downstream MAPK pathway dysregulation and identified Dabrafenib — a selective BRAF inhibitor — as the top mechanistically coherent candidate. Inference chain:
1
BRAF V600E mutation detected — constitutively active BRAF kinase. V600E accounts for ~8–10% of colorectal cancer cases and is associated with poor prognosis in MMR-proficient disease.
PMIDs: 22448344, 20619739
2
MAPK pathway hyperactivation — BRAF V600E drives MEK/ERK signaling independent of RAS, creating a targetable dependency distinct from KRAS-driven CRC.
PMIDs: 41072415, 24265154
3
Dabrafenib scored Tier I candidate — BRAF inhibitor with established clinical evidence in melanoma and NSCLC (V600E). Colorectal context noted with feedback reactivation caveat; combination with cetuximab highlighted.
PMIDs: 23020132, 29573941
4
Confidence: 70% — driven by target-in-panel match, cross-indication BRAF V600E evidence, pathway coherence, and 6 PubMed citations at analysis time.
Domain Intelligence
Why BRAF Inhibitors Alone Fail in CRC
GaiaLab's inference chain surfaced a critical caveat that separates CRC from melanoma despite the same V600E mutation: EGFR-mediated feedback reactivation.
⚠ EGFR feedback reactivation — BRAF V600E CRC vs melanoma
!
In melanoma, BRAF inhibition suppresses the MAPK cascade durably. In CRC, EGFR is highly expressed on the cell surface. BRAF inhibition triggers relief of negative feedback on RAS → EGFR-driven reactivation of MEK/ERK within hours, making single-agent BRAF inhibition largely ineffective.
PMID: 23833300
→
Clinical implication: The BEACON-CRC trial (NCT02928224) validated this biology — Encorafenib + Binimetinib + Cetuximab (BRAF + MEK + EGFR blockade) achieved a 26% ORR vs 2% for single-agent BRAF inhibition in BRAF V600E CRC. GaiaLab's analysis flagged cetuximab combination precisely because of this feedback mechanism.
PMID: 31566309
↗
Dabrafenib in this context: As a selective BRAF inhibitor, Dabrafenib faces the same feedback reactivation. Combination with Trametinib (MEK) and Cetuximab (EGFR) is the clinically rational extension — and exactly the regimen being tested in NCT06978400 (registered May 2025).
Clinical Validation
Confirmed Trials on ClinicalTrials.gov
GaiaLab's automated ledger cross-referenced this prediction against ClinicalTrials.gov and found 5 registered trials for Dabrafenib in colorectal cancer. All trials predated the Feb 23 2026 prediction — these are retrospective co-occurrences, not prospective confirmations.
NCT03668431
BRAF-targeted therapy in colorectal cancer
NCT01750918
Dabrafenib in BRAF-mutated solid tumors including CRC
NCT06967155
BRAF inhibitor combination in colorectal cancer
NCT06978400
Dabrafenib-based regimen in colorectal cancer · first posted 2025-05-18 (9 months before prediction)
All 5 NCT IDs verified against ClinicalTrials.gov API v2 · 2026-05-22. NCT06978400 first posted 2025-05-18 — predates the Feb 23 2026 prediction; classified as retrospective co-occurrence, not prospective confirmation.
Accuracy Context
How Accurate Is GaiaLab for Colorectal Cancer?
This case is not cherry-picked. Full population-level performance for colorectal cancer in the GaiaLab ledger:
0.7469
CRC-specific AUROC (n=731 predictions)
vs 0.544 platform average · vs 0.50 random baseline. Colorectal cancer is one of GaiaLab's highest-performing disease contexts.
5
ClinicalTrials.gov co-occurrences for this drug-disease pair
Co-occurrence = GaiaLab drug appears in a registered CRC trial. All are retrospective — trials predated the Feb 23 2026 prediction.
Full calibration curve and per-disease AUROC: validation page →
What We're Building Next
Prospective Validation — In Progress
We are building genuine prospective validation: predictions timestamped before a trial registers. The infrastructure is live — every new analysis is recorded with a timestamp and automatically checked against ClinicalTrials.gov weekly. As trial registration dates are captured for new predictions, this page will be updated with verified prospective cases.
Current limitation: The trial registration dates for the 5 confirmed trials above were not captured at prediction time. We therefore cannot confirm that this specific prediction preceded any of these specific trial registrations. We will not claim that until the data proves it.
GaiaLab predictions are computational hypotheses grounded in public literature and pathway data. They are not medical advice. The 80% confidence score reflects the strength of computational evidence at analysis time, not the probability of clinical success.
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