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Colorectal Cancer Biomarker Cheat Sheet

Essential biomarkers for CRC patients — mutations that block therapy, markers that unlock immunotherapy, and emerging MRD monitoring.

BiomarkerWhat It Tells YouTypeTreatment Implications
KRAS / NRAS RAS pathway mutations (~50% of CRC) Exclusionary RAS mutant: anti-EGFR therapy (cetuximab, panitumumab) will NOT work. RAS wild-type: eligible for anti-EGFR
BRAF V600E Aggressive tumor biology (~8–12%) Targeted Encorafenib + cetuximab (Braftovi + Erbitux); poor prognosis marker
MSI / MMR Mismatch repair deficiency (~15% stage II–III) Immuno MSI-H/dMMR: checkpoint inhibitors (pembrolizumab, nivolumab ± ipilimumab); may not benefit from 5-FU adjuvant
HER2 (ERBB2) Amplification/overexpression (~3–5%) Targeted Trastuzumab + pertuzumab, trastuzumab deruxtecan (Enhertu); requires RAS wild-type
NTRK Fusion Rare oncogenic driver (<1%) Targeted Larotrectinib (Vitrakvi), entrectinib (Rozlytrek) — tissue-agnostic approval
TMB Tumor mutation burden Immuno TMB-High (≥10 mut/Mb): pembrolizumab (tissue-agnostic); less predictive in CRC than MSI
ctDNA / MRD Circulating tumor DNA for minimal residual disease Monitoring Post-surgery ctDNA+ predicts recurrence; emerging role in guiding adjuvant therapy decisions
CEA Carcinoembryonic antigen blood marker Monitoring Used for surveillance post-treatment; rising CEA may indicate recurrence
Key Point: All metastatic CRC patients should have extended RAS (KRAS/NRAS) and BRAF testing before starting first-line therapy. MSI/MMR status should be tested in all CRC patients regardless of stage — it guides both treatment and Lynch syndrome screening. Comprehensive genomic profiling can identify additional targets like HER2 and NTRK in one test.

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