NRAS

What is the NRAS biomarker?

The NRAS gene is present in each of the cells in our body. The gene holds the instructions for
making a protein by the same name, NRAS. The normal (wild type) NRAS protein is inside each
cell and teams up with a group of proteins (the EGFR/RAS/MAPK pathway) as an “on/off” switch
to monitor cell growth, division, and movement. The cancer-causing variations (mutations) in the
NRAS gene cause abnormal NRAS proteins that are locked in the “on” position and drive constant
and uncontrolled cell division.1,2

What does NRAS mutation mean?

A NRAS gene mutation is A NRAS mutation is NOT hereditary

The mutation happens (not a germline mutation) and will NOT
found in about
early, when the cancer pass from one generation to another.
starts to develop, driving
In all cases, a NRAS mutation happens
uncontrolled growth.
5% This is called a
randomly and it is a somatic mutation.
The most common mutations in
NRAS gene are G12D, G12C, Q61K,
driver mutation. and Q61R.1-3
of colorectal cancer
patients.1

When and how should I have NRAS biomarker testing?

All patients diagnosed with stage IV, metastatic colorectal cancer and those who have a
recurrence should be tested for NRAS mutation as part of the RAS panel testing. This is
recommended by the National Comprehensive Cancer Network (NCCN) and the American
Society of Clinical Oncologists (ASCO). Patients should also test for NRAS mutations before
starting anti-EGFR therapy.4-6 Testing can be done on the tumor as part of a comprehensive
molecular (biomarker) test.

What do I do with this information?

Knowing the details of tumor biomarkers can help you and your doctor make decisions about
personalized treatment with therapies tailored to the characteristics of your tumor.

 A mutation in the NRAS gene is also a negative predictive biomarker for a poor response
to anti-EGFR treatments like cetuximab or panitumumab and therefore, patients with a NRAS
mutation should not receive anti-EGFR drugs alone or in combination with chemotherapy.4,5

continued 4
What treatment options are available?
Patients with NRAS-mutated colorectal cancer should receive chemotherapy (some examples are
FOLFOX, CAPOX, and FOLFIRI), with or without Bevacizumab (an antibody that inhibits the growth
of blood vessels and oxygen supply in the tumor).

There is currently no specific anti-NRAS therapy but there are ongoing clinical trials with new
KRAS/NRAS inhibitors.7

What are the potential side effects of treatment?

Every treatment has the potential to cause some side effects. Some people may be more sensitive
than others to a particular drug. The response to a specific treatment also depends on your
medications, vitamins and herbal supplements. Tell your doctor and pharmacist about all of your
medications, vitamins, and treatments. If you are experiencing severe side effects, call your
doctor immediately.

For more on side effects of other chemotherapy regimens: ccalliance.org/colorectal-cancer-

information/treatments/side-effects

For additional questions and assistance: ccalliance.org/patient-family-support/helpline

For our Clinical Trial Finder: ccalliance.org/ctf

1
Dekker E et. Al., Colorectal Cancer 2019 The Lancet 394: 1467-1480
2
DeStefanis RA et al Targeted therapy in metastatic colorectal cancer: current standards and novel agents in review 2019 Current Colorectal Cancer Reports 15: 61-69
3
Vanderbilt-Ingram Precision Medicine program http://mycancergenome.org
4
NCCN clinical cancer practice guideline in oncology (NCCN Guidelines) Ver.4-Nov 8, 2019 http://nccn.org/professionals/physician_gls/pdf/colon.pdf
5
NCCN clinical cancer practice guidelines in oncology (NCCN Guidelines) Ver.3-Sep 26, 2019 https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf
6
Sepuldeva AR et al, Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline from the American Society for Clinical Pathology, College of American
Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. 2017 J. Clinical Oncology 35:1453-1486
7
Porru M et al, Targeting KRAS in metastatic colorectal cancer: current strategies and emerging opportunities 2019 J. Exp and Clinical Cancer Research 37;35

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