A biomarker (also called a biological marker) is a piece of information about your health. Biomarkers include your blood pressure, your blood type, and cholesterol or blood sugar levels measured in a blood test. The biomarkers of cancer are also known as tumor markers. Biomarkers can tell your medical team important information about you and your cancer.

What is a colorectal cancer biomarker?

For colorectal cancer (which refers to colon cancer, rectal cancer, and bowel cancer), relevant biomarkers include:

Why are biomarkers important?

Colorectal cancer biomarkers can provide your medical team vital information about you and your cancer that is used to determine prognosis, guide treatment decisions, monitor treatment response, and look for recurrence after treatment. Biomarkers are also used in drug development to create and test targeted therapies for colorectal cancer.

How are biomarkers and biomarker
testing used?

Colorectal cancer biomarkers can provide your medical team vital information about you and your cancer that is used to determine prognosis, guide treatment decisions, monitor treatment response, and look for recurrence after treatment. Biomarkers are also used in drug development to create and test targeted therapies for colorectal cancer.

Prognosis

Prognosis is the expected course of a disease. Biomarkers can indicate the overall prognosis of your cancer and your risk of cancer recurrence after treatment.

Treatment Decisions

Some predictive biomarkers can indicate which treatments will be effective or ineffective against your cancer. Other biomarkers can predict which treatments will cause you severe toxic side effects. Biomarkers that predict recurrence after treatment may guide decisions about adjuvant therapy after surgery.

Treatment Response Evaluation

Some biomarkers can be used as surrogate endpoints, which are indicators of how well a treatment is working. Surrogate endpoints are often examined in the short-term setting of clinical practice or clinical trials to predict long-term outcomes like survival or disease progression. In clinical care, measuring a biomarker surrogate endpoint may lead to earlier changes in a treatment that is not working. In clinical trials, surrogate endpoint measurement may allow faster drug approval by regulatory bodies like the U.S. Food and Drug Administration (FDA) or European Medicines Agency (EMA).

Screening and Recurrence Monitoring

Biomarkers can be used to screen for cancer in people who are at high risk for cancer and can be used in follow-up care to look for recurrence after treatment. New biomarkers are under investigation for the screening of patients with average colorectal cancer risk.

Treatment Development

Biomarkers are used to identify potential targets of colorectal cancer treatments. These targets are often mutations in the genes that encode (provide the instructions for making) enzymes and other proteins involved in abnormal growth and tumor spread. New targeted therapies that disrupt the processes (molecular pathways) of abnormal growth are studied through clinical trials. Clinical trials of cancer treatment always compare new treatments to the standard clinical practice, never a non-treatment placebo.

What is a biomarker test?

A biomarker test is a laboratory test for a genetic mutation in your tumor cells or in your other cells, a measurement of the presence or amount of a substance (DNA or protein) in your tumor tissue or blood, or an imaging test (like a CT scan) of your tumor.

How are biomarkers tested?

Biomarker testing is done by analyzing tumor biopsy tissue, blood samples, or other body fluids. When biomarkers are tested in circulating tumor DNA (ctDNA) from a blood sample, it is called liquid biopsy. Biomarker information can also come from radiologic imaging (CT scans, X-rays, MRI scans), or surgical reports.

What types of biomarkers can be tested in colorectal cancer patients?

Colorectal cancer biomarkers that give prognostic information, help guide treatment decisions, and allow monitoring for treatment response or recurrence after treatment 

Biomarkers of hereditary colorectal cancer

The biomarkers that can confirm hereditary colorectal cancer are the DNA mismatch repair genes causing Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer), and the genes causing Familial Adenomatous Polyposis (FAP) and associated syndromes. Lynch Syndrome is caused by mutations in MLH1, MSH2, MSH3, MSH6, EPCAM, or PMS2 genes, while FAP and other polyposis syndromes are caused by mutations in APC, MYH, BMPR1A, and SMAD4.

Lynch Syndrome

Learn about Lynch Syndrome, also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC), a cancer syndrome caused by deficient DNA mismatch repair (dMMR).

Familial Adenomatous Polyposis (FAP)

Learn about familial adenomatous polyposis (FAP), an inherited genetic colorectal cancer syndrome, and how it affects you and your family.

Treatment toxicity biomarkers

Treatment toxicity biomarkers that can be tested to give you and your healthcare team information about the risk of severe or life-threatening side effects from cancer drugs. These are UGT1A1, an enzyme needed for metabolism of fluorouracil (5-FU) based chemotherapy drugs and DPYD, an enzyme required for metabolism of irinotecan and irinotecan-related chemotherapy drugs.

Who should have biomarker testing?

Everyone with colorectal cancer should have biomarker testing.  

The exact biomarker tests needed can vary by:  

All CRC patients, no matter the stage at diagnosis, should be tested for microsatellite stability / instability (MSS / MSI) biomarker testing. [Recommended by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO).]

If you have stage IV / metastatic colorectal cancer, you should have testing for RAS (both KRAS and NRAS), and BRAF. [Recommended by NCCN and ESMO.]

If you have stage IV / metastatic colorectal cancer you should have HER2 testing. [Recommended by NCCN.]

There are several biomarkers that don’t currently have standardized recommendations for testing, including PIK3CA, tumor mutational burden (TMB), and NTRK gene fusion. Talk to your healthcare team about whether testing these or other specific biomarkers could help you.