KRAS Biomarker

The KRAS gene is responsible for the production of the K-Ras protein. The protein acts as an 
“on-off” switch that instructs cells to grow and divide or mature and take on different functions. The KRAS gene is an oncogene because when it is mutated or changed it can cause normal cells to become cancerous. KRAS is a member of the RAS family of genes that include NRAS and HRAS. These are important in cell growth, formation of cancer, and cell destruction (apoptosis). K-Ras is an important part of the RAS/MAPK pathway. There are several drugs being investigated that work on different components of the pathway.

Experts recommend that anyone with stage IV or metastatic colorectal cancer (mCRC) be tested for multiple genetic (genomic) mutations including KRAS and NRAS. RAS status must be determined prior to the start of any EGFR-inhibitors. Biomarker testing should be done on the primary tumor and any subsequent metastases with comprehensive genomic testing.

Knowing your biomarker status will guide you and your doctor as you choose a treatment plan that will work best for your cancer.

• A mutation in the KRAS gene is a predictive biomarker for a poor response to EGFR-inhibitors. Therefore, patients with a KRAS mutation or unknown KRAS status should not receive EGFR-inhibitors like cetuximab or panitumumab alone or in combination with chemotherapy.
• Patients with mutated or unknown KRAS or NRAS status should receive chemotherapy including FOLFOX, CAPOX, or FOLFIRI with or without bevacizumab (an antibody that inhibits the growth of blood vessels and oxygen supply in the tumor).

Currently, there are no specific anti-KRAS therapies but there are ongoing clinical trials looking at potential KRAS 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.