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.

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. Testing can be done on the tumor as part of a comprehensive molecular (biomarker) test.

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

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.

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 other treatments (for example, radiation) and medications. It may also depend on 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, click here.