John Tentler, Ph.D.
Associate Professor of Medical Oncology
University of Colorado School of Medicine

Guest blogger, John Tentler, Ph.D. from the University of Colorado School of Medicine highlights the importance of biomarkers in colorectal cancer treatment decisions with the hope of advancing the science as researchers have in other cancers.

All Cancers are Not the Same

With the emergence of new technologies, such as next generation DNA sequencing, the complex molecular landscapes of cancer are being revealed and it is becoming ever more apparent that all cancers are not the same, even within a particular cancer type.

Indeed, it has long been appreciated that there are several types of breast cancer, with further subtypes within those categories. These discoveries have in turn dramatically changed oncology practice with regard to diagnosis, prognosis, and treatment decisions. For example, all breast cancer patients are now routinely tested for expression of the estrogen receptor, progesterone receptor and HER2 to guide treatment options. These genes are examples of biological markers, or “biomarkers,” which are increasingly being used by oncologists to stratify patients into subgroups to help guide treatment strategies, effectively implementing a “personalized medicine” approach.

Colorectal Cancer Biomarkers

More recently, concerted efforts have been directed towards identifying predictive biomarkers of response to therapeutics in colorectal cancer (CRC), some of which are now being incorporated into oncology practice. Currently, the following biomarkers are being used to guide treatment decisions for CRC patients:

The RAS oncogenes: KRAS and NRAS

Most frequently mutated genes in CRC, with KRAS in up to 50% of cases.

RAS is a molecular on/off switch regulating a key pathway controlling cell division.

Typically RAS is activated by a cell surface receptor such as the epidermal growth factor receptor or EGFR. However, if RAS is mutated it is stuck in the “on” state and therapies directed at EGFR such as cetuximab and panitumumab will be ineffective as EGFR is no longer controlling RAS.


Another signaling enzyme downstream of RAS in this pathway is BRAF (pronounced B-RAF).

While mutations in BRAF are less common than RAS, it is a biomarker of poor prognosis in CRC. Because of this, more aggressive chemotherapy regimens, as well as surgery and radiation may be considered.


Patients who have microsatellite instability or MSI (high) have a defect in normal DNA repair mechanisms that result in high mutation rates.

A patient with MSI may have Lynch syndrome which needs to be confirmed by formal laboratory testing.

If the MSI CRC patient is stage II or III, the prognosis is better and they may not benefit from adjuvant (additional) chemotherapy such as 5-FU. If they are MSI and stage IV, studies have shown that they may be responsive to immunotherapies, such nivolumab (anti-PD-1).


Finally, PI3 kinase (PI3CK) mutations are present in approximately 15-20% of colorectal cancers. Studies have indicated that these patients may benefit from aspirin therapy following surgical resection. However, testing for this mutation is not standard of care at present.

It should be noted that while these biomarkers have resulted in more effective and longer-lasting responses to therapies, not all patients will respond predictably to treatment.

Despite our advances in biomarker discovery in CRC, ongoing research is actively seeking to identify additional markers to bring this disease to the point that breast oncology has reached. We anticipate further study results of predictive biomarkers to best identify individuals who will benefit from specific forms of treatment. The breast cancer community has done an excellent job with standardizing biomarker testing to make it widely uniform and available for patients. By learning from these successes, we hope to make these advances a reality in the CRC community.

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4 comments on “Biomarkers Help Guide Treatment Decisions for Colorectal Cancer Patients”

  1. 1
    Sharyn on February 25, 2019

    Hi Solveig, We cannot give medical advice. However, you can find more information about MSI/MSS and out trial finder here: https://fightcolorectalcancer.org/fight/diagnosis/what-is-msi-and-mss/ And check out the biomarked site as well which is being updated regularly to include biomarkers being studied in CRC: https://fightcolorectalcancer.org/biomarked/ Finally, if you have specific questions about your treatment plan, talk to your doctor and don’t hesitate to get a second opinion!

  2. 2
    Solveig karlsen on February 20, 2019

    I have metastatic (spread to liver) anal cancer and tested MSI low (negative). Will I have effect of immuntherapy, or should I be tested for other bio markers. I have heard that there is no hope for treatment other than chemotherapy When i am msi-low.

  3. 3
    Carol Bowser on April 1, 2016

    My doctor wants me to start taking Lonsurf as other chemos are no longer working. My cost for this is $3000 per cycle which is unaffordable for me. From what I have read, it doesn’t appear to be that helpful anyway. What are your thoughts on this?

    1. 4
      Andrew Wortmann on April 5, 2016

      Hi Carol, We’re aren’t able to give out medical advice. If you’re unsure of what your doctor is recommending, a second opinion is always available from another doctor.

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