When you’re diagnosed with colorectal cancer (CRC), one of the most important steps you and your care team can take is biomarker testing. Biomarkers are molecules, including genes and proteins, that provide information about your specific cancer. Testing for these biomarkers helps your doctor understand what’s driving your cancer’s growth and spread, so your treatment plan can be tailored to target it more precisely.

Biomarker testing can open the door to more effective, personalized treatment options, including targeted therapies and immunotherapies that may work better for your cancer type. It’s recommended for all stages of CRC, not just advanced disease, because it can influence both current treatment decisions and future care if the cancer returns or spreads.

Germline vs. somatic mutations: What’s the difference?

When we talk about cancer-related genetic changes, there are two main types: germline mutations and somatic mutations.

• Some germline mutations are associated with hereditary (familial) cancers and inherited disorders and can increase your lifetime risk of developing CRC or other cancers.
• Somatic mutations, on the other hand, occur after birth and are only found in the cancer cells themselves. They aren’t inherited or passed on to children.

Approximately 95% of CRCs are caused by somatic mutations, meaning they develop due to changes in the DNA of the colon or rectal cells over time rather than inherited genetic traits. Understanding which type of mutation you have helps your doctor determine the most effective treatments and whether your family members might need genetic counseling.

How is biomarker testing done?

Biomarker testing can be performed in different ways:

• Tissue biopsy: A small sample of the tumor is taken during surgery or another procedure and tested in a lab to identify key mutations or proteins.
• Liquid biopsy: A simple blood test that looks for fragments of tumor DNA circulating in your bloodstream (known as circulating tumor DNA, or ctDNA).

Both types of tests can provide valuable information about your cancer’s characteristics and how it may respond to certain treatments.

Common biomarkers tested in CRC

Regardless of stage, all patients with CRC should be tested for high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR).

These tests look at how well your cells repair DNA damage. Tumors that are MSI-H or dMMR have a harder time fixing DNA mistakes, which can lead to more mutations. About 1 in 6 CRCs are MSI-H or dMMR, and identifying this biomarker early is important because these tumors may respond especially well to immunotherapy.

Your doctor may also test certain prognostic biomarkers during routine follow-up care—most commonly carcinoembryonic antigen (CEA).

CEA is a protein that can sometimes be found at higher levels in people with CRC. Monitoring CEA levels can:

• Confirm whether the cancer has returned (recurrence)
• Show how well treatment is working
• Guide future treatment decisions

For stage IV (metastatic) CRC

Patients diagnosed with stage IV CRC should be tested for at least four key predictive biomarkers:

• RAS (KRAS and NRAS): With KRAS or NRAS mutations, certain targeted therapies are less likely to work. Knowing your RAS status helps your doctor avoid treatments that won’t be effective.
• BRAF mutations: Up to 12% of CRCs have a BRAF mutation, most commonly BRAF V600E, which can make the cancer more aggressive. Patients with this mutation may benefit from specific targeted therapies designed to block BRAF signaling pathways.
• HER2 amplification: If your cancer is HER2-positive, it may respond to HER2-targeted treatments.

Information about these biomarkers helps your care team choose the most effective treatment options that’s personalized to your own diagnosis. 

Biomarker testing for treatment resistance and recurrence

Biomarker testing isn’t just conducted at the time of diagnosis. If your current treatment plan stops working or if your cancer has come back, biomarker testing can help identify new mutations that may have developed and point to different treatment options. It’s a critical part of assessing next steps for your care.

If you or a loved one has been diagnosed with CRC, make sure to have a discussion with your care team about biomarker testing.

Join the Outcomes4Me Community for a safe space to share your story and connect with others who share your diagnosis.