CancerDrs

Biomarkers

Colorectal Cancer biomarkers — what to test

Colorectal cancer has well-established biomarkers that should be tested for every advanced-stage case and many early-stage cases. KRAS, NRAS, BRAF, MSI/MMR, and HER2 testing are now standard. Testing matters before first-line therapy — for example, anti-EGFR drugs don't work in RAS-mutant tumors.

Standard biomarkers

These are typically tested on every new diagnosis, or required before systemic therapy decisions, under current U.S. clinical guidelines.

MSI / MMR (Microsatellite Instability / Mismatch Repair)

Standard

What it is: Either tested by IHC (for MMR proteins MLH1, MSH2, MSH6, PMS2) or PCR/NGS (for MSI). Either test tells you the same thing.

Why test: MSI-H / dMMR tumors respond well to immune checkpoint inhibitors. Also signals possible Lynch syndrome (hereditary cancer). Guidelines recommend universal testing of all colorectal cancers.

Therapies it unlocks:
  • Pembrolizumab (Keytruda) as monotherapy for MSI-H/dMMR CRC
  • Nivolumab ± ipilimumab
  • Dostarlimab (Jemperli)

KRAS / NRAS

Standard

What it is: Mutations in the RAS oncogenes. Most common codons: KRAS G12, G13, Q61; similar for NRAS.

Why test: RAS-mutant colorectal cancers do NOT benefit from EGFR-targeted antibodies (cetuximab, panitumumab). Testing is required before first-line therapy for metastatic disease.

Therapies it unlocks:
  • If RAS wild-type: cetuximab or panitumumab + chemotherapy
  • If KRAS G12C specifically: sotorasib or adagrasib (newer use)

BRAF V600E

Standard

What it is: BRAF V600E mutation, found in ~8-10% of metastatic CRC.

Why test: BRAF-mutated CRC has worse prognosis on standard chemo but responds to specific BRAF + EGFR combinations.

Therapies it unlocks:
  • Encorafenib + cetuximab
  • Encorafenib + cetuximab + binimetinib in some settings

Context-specific biomarkers

Tested depending on cancer stage, subtype, family history, or as part of broader NGS (next-generation sequencing) panels.

HER2

What it is: HER2 amplification, less common than in breast/gastric but actionable when present.

Why test: HER2+ metastatic CRC has newer targeted options.

Therapies it unlocks:
  • Tucatinib + trastuzumab
  • Trastuzumab deruxtecan

Lynch syndrome / Germline testing

What it is: Inherited MLH1, MSH2, MSH6, PMS2, or EPCAM mutations.

Why test: Lynch-associated CRC often presents young, often is MSI-H, and has implications for family members. All patients with MSI-H CRC (and all CRC under age 50) should be offered germline testing.

Therapies it unlocks:
  • (Therapy decisions same as MSI-H path) plus surveillance and risk-reduction for patient + family

NTRK / RET / FGFR / others

What it is: Rare targetable alterations found on comprehensive NGS panels.

Why test: Tumor-agnostic therapies exist for NTRK fusions and some others. Comprehensive panels may surface these.

Therapies it unlocks:
  • Larotrectinib, entrectinib (NTRK fusion)
  • Selpercatinib, pralsetinib (RET fusion)

Questions to ask your oncologist

  • What biomarker testing are you doing on my tumor?
  • Are there any tests we are skipping that I should consider?
  • Will we wait for results before starting systemic therapy, or start something interim?
  • Is germline genetic testing appropriate for me, given my personal and family history?
  • If a biomarker test is indeterminate, what is the plan?

Next steps

FDA-approved colorectal cancer drugs →

See which FDA-approved drugs match each biomarker profile above.

 Colorectal Cancer clinical trials →

Active recruiting trials, many biomarker-matched.

 Biomarkers explained: full guide →

Deeper background on how biomarker testing works.

 Germline genetic testing →

Different from tumor testing; addresses inherited cancer risk and family implications.

 Genetic testing cost →

What germline and tumor molecular tests cost, and how insurance covers each.

 BRCA test cost →

What patients pay in practice for BRCA1/2 testing and ACA preventive coverage rules.