Colorectal Cancer and Tumor Markers

What are tumor markers?

Tumor markers are biochemical substances that may be detected in your blood, urine, or body tissues by laboratory tests. They are produced by cancer cells, or by your body’s response to cancer or certain noncancerous disorders.

Different types of cancer are characterized by different tumor markers. However, many tumor markers are found in more than one type of cancer. Hundreds of potential tumor markers have been identified and studied by researchers, although the number of tumor markers in practical clinical use is much smaller. Cancers associated with known tumor markers include colorectal cancer and cancer of the breast, prostate, liver, and pancreas.

Tumor Markers for Colorectal Cancer

Doctors use tumor markers to detect, diagnose, and manage certain types of cancer. In colorectal cancer, tumor markers are used specifically to help doctors monitor patients after treatment. However, there are important limitations on their use.

Not all patients with colorectal cancer produce these markers, and it is possible for other types of diseases (or even chemotherapy itself) to increase marker levels. For this reason, doctors generally use tumor markers only in combination with other methods (such as imaging tests) for monitoring response to treatment in patients with colorectal cancer.

Doctors also test patients both before and after treatment to make sure they can identify and interpret changes in tumor marker levels accurately. Tumor markers are currently best used to assess response to treatment. It is not yet possible to use currently known tumor markers to screen patients for colorectal cancer.

Doctors eventually hope that by simply examining a patient’s tumor markers that they will be able to predict in advance whether a patient’s cancer will respond to the therapy being considered. Armed with a better understanding of how colorectal cancer cells function, researchers could more easily find out which treatments are most effective in killing them, and why. Eventually, it may be possible for doctors to combine this information with the results of genetic testing to completely “personalize” your treatment, making it as effective, safe, and well-suited to you as it can be.

How are tumor markers used today to help people with colorectal cancer?

For patients with advanced or metastatic colorectal cancer, carcinoembryonic antigen (CEA) testing is used after surgery or during chemotherapy as one way to find out whether the cancer has returned or has begun to spread.

Using CEA to Find Out If Treatment Is Working

CEA is a protein and well-known colorectal tumor marker that was first discovered in 1965. A positive blood test for high or increasing levels of CEA suggests that colorectal cancer may be present (or may be spreading), but it could also be caused by other diseases. CEA testing is useful for following up certain patients who have been diagnosed with colorectal cancer that has spread to the outer layers of the colon or beyond the colon, after these patients have received treatment.

Doctors may use CEA to help detect any signs that the colorectal cancer has come back, or has spread further after treatment. This allows doctors and patients to act quickly in making decisions about further treatment. However, only patients with CEA-producing colorectal cancers can be monitored in this way, and doctors use CEA in combination with other methods for monitoring patients. 

Recommended Uses for CEA: After Surgery

The American Society of Clinical Oncology (ASCO), the leading professional organization representing physicians who treat people with cancer, recommends using CEA testing to help determine whether colorectal cancer persists and has spread after surgery. Patients with Stage II or Stage III colorectal cancer should receive CEA testing every 3 months after surgery, for at least 3 years. If the patient is receiving chemotherapy after surgery, testing should wait until after chemotherapy is completed.  

Recommended Uses for CEA: During Chemotherapy

For patients with metastatic colorectal cancer, ASCO recommends testing for CEA every 1 to 3 months to determine whether treatment is working or whether the cancer has spread. Depending on the level, your doctor may recommend additional tests. To be sure of their information, doctors are generally not advised to use CEA levels as their only evidence supporting the conclusion that colorectal cancer has come back or has spread.

What other tumor markers have been investigated for use in colorectal cancer?

CA 19-9 as a Marker

Carbohydrate antigen 19-9 (CA 19-9) is another well-known molecule that was first identified as a colorectal tumor marker in 1979. CA 19-9 may be used as a tumor marker for cancer of the pancreas. However, for colorectal cancer, there is not enough evidence currently to suggest that it is useful for finding out whether treatment is working or whether the cancer has spread.

EGFR as a Marker

Epidermal growth factor receptor (EGFR) has been studied as a marker that may predict how well a patient may do after being diagnosed with colorectal, lung, and breast cancer. EGFR is also a target for treating colorectal cancer because its overactivity could promote cancer cell growth. 

P53 and ras (KRAS) as Markers

Researchers have studied the p53 gene (a cancer-inhibiting gene) and the ras (also called the K-ras or KRAS) gene, as well as the APC gene, in colorectal cancer. Damaged or mutated versions of these genes can change a cell’s function and make it easier for the cell to become cancerous. Researchers would like to understand how this happens, and what biochemical and genetic processes the cancer cell depends on. This makes it easier to develop new, more effective treatments for colorectal cancer.

Chromosome and Cellular DNA Markers

Investigators have explored how damage to chromosomes 5q, 8p, and 17p, which means loss or damage to the genes in those areas, could lead to the development of colorectal cancer. Scientists have also measured the amount of DNA (genetic material) in cancer cells (testing for DNA ploidy) and recorded the patterns of DNA in blood samples from patients with colorectal cancer (this is called testing for microsatellite instability). These studies may eventually lead to a better understanding of colorectal cancer or new ways to predict which patients are most likely to have better survival rates.

How can genetic tumor markers help patients with colorectal cancer?

One example of the value of genetic tumor markers involves the KRAS gene, EGFR, and drug treatments for colorectal cancer called EGFR inhibitors. Recently, researchers have reported that the presence or absence of a mutated copy of the KRAS in colorectal cancer cells makes a difference in whether patients will respond well to an EGFR inhibitor.

Studies show that patients who have colorectal tumors without the mutated version of the KRAS gene are much more likely to respond to drugs such as Vectibix™ (panitumumab) or Erbitux^® (cetuximab), which are two EGFR inhibitors. This makes it possible to use KRAS as a marker for the ability to respond to treatment with EGFR inhibitors. Since most effective treatments for cancer have serious side effects and are expensive, it is important for a person with colorectal cancer to know as early as possible whether a particular treatment may be useful or not.

The National Cancer Institute (NCI) database currently lists more than 100 ongoing clinical research projects involving tumor markers and colorectal cancer. Ideally, these studies or others like them will reveal how people with colorectal cancer can best benefit from the use of tumor markers.