NRAS biomarker and colorectal cancer
What is the NRAS biomarker?
NRAS is a gene that helps control how cells grow and divide. It is part of the RAS family of genes, which also includes KRAS and HRAS.
Normally, the NRAS protein acts like an “on-and-off switch” for cell growth. An NRAS mutation can cause the switch to remain turned on, sending continuous signals that encourage cancer cells to grow.
An NRAS mutation is called a driver mutation because it can contribute to the development and growth of a tumor.
How common are NRAS mutations?
NRAS mutations are less common than KRAS mutations and are found in approximately 3% to 7% of colorectal cancers. Changes may occur in several areas of the NRAS gene, including codons 12, 13, 59, 61, 117, and 146.
The NRAS mutation identified through colorectal cancer biomarker testing is usually a somatic mutation. This means it developed in the tumor and is not generally something a person was born with or can pass to their children.
Tumor biomarker testing is different from testing for inherited cancer risk. Your care team may recommend separate genetic counseling or germline testing based on your diagnosis and family history.
What does NRAS wild-type mean?
An NRAS wild-type result means the laboratory did not find a tested mutation in the NRAS gene.
However, NRAS is only one part of RAS testing. A tumor is considered RAS wild-type only when no relevant mutations are found in either KRAS or NRAS.
This distinction is important because medicines that target EGFR are generally used only when the tumor is RAS wild-type.
Who should have NRAS and RAS testing?
People with metastatic colorectal cancer (stage IV) should have their tumors tested for both KRAS and NRAS mutations.
Testing should ideally occur before treatment decisions are made, particularly before considering anti-EGFR medicines such as cetuximab or panitumumab. Comprehensive RAS testing examines clinically important areas of KRAS and NRAS, including exons 2, 3, and 4.
Testing may be performed using tumor tissue, a blood-based liquid biopsy or a broad biomarker panel.
Video: understanding RAS mutations
What treatment options are available?
Your complete RAS result helps your care team decide whether certain targeted treatments may work.
If the tumor has an NRAS mutation, anti-EGFR medicines such as cetuximab and panitumumab are generally not recommended because RAS mutations predict resistance to these treatments.
Treatment may instead include chemotherapy, medicines that target tumor blood vessels, surgery or other local treatments when appropriate, and treatments selected according to other biomarkers such as MSI/MMR, BRAF, HER2, or NTRK.
There is currently no FDA-approved treatment that directly targets an NRAS mutation in colorectal cancer. However, treatment research is expanding, and clinical trials may provide access to medicines designed to block NRAS, several RAS proteins, or related cell-growth pathways.
If no mutation is found in either KRAS or NRAS and the tumor is RAS wild-type, cetuximab or panitumumab may be a treatment option. In first-line treatment, anti-EGFR therapy is most strongly supported for certain patients whose metastatic colorectal cancer began on the left side of the colon or in the rectum.
Clinical trials for NRAS-mutated colorectal cancer
Clinical trials are especially important for people with NRAS-mutated colorectal cancer because there is not yet an approved medicine that directly targets NRAS.
Researchers are studying:
- Medicines designed to block multiple RAS proteins
- Treatments that interrupt signals NRAS uses to help cancer cells grow
- Combinations that target several cancer-growth pathways
- Immune-based treatments
- New approaches intended to overcome resistance to treatment
Ask your doctor about clinical trials at diagnosis of metastatic disease and whenever treatment is being started or changed. Eligibility may depend on the exact NRAS mutation, other biomarker results, previous treatment, and overall health.
Questions to ask your doctor
- What exact NRAS mutation was found?
- Were both KRAS and NRAS fully tested?
- Is my tumor RAS-mutated or RAS wild-type?
- Were other important biomarkers tested?
- How does my RAS result affect the use of cetuximab or panitumumab?
- Are there clinical trials for my exact mutation?
- Should my tumor be tested again if the cancer changes or stops responding to treatment?
This content was developed with support from
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