KRAS biomarker and colorectal cancer

KRAS is a member of the RAS family of genes that include NRAS and HRAS.

A normal KRAS gene teams up with a group of proteins as an “on/off” switch to monitor cell growth. An abnormal mutation in the KRAS gene happens early in the development of cancer.

This abnormality is known as a driver mutation because it causes the switch to be locked in the “on” position and drives uncontrolled cell growth, leading a tumor to form.

Approximately 40-45 percent of colorectal cancer patients have a KRAS mutation in their tumor.

A KRAS mutation is not hereditary (a germline mutation) and will not be passed from one generation to another in a family.

All KRAS mutations happen randomly and are somatic or non-hereditary mutations. The most common KRAS mutations are G12V, G12D, G14D, G12C, and G12A.

Patients with stage IV (metastatic) colorectal cancer should be tested for KRAS mutations.

KRAS status must be determined prior to the start of any EGFR-inhibitors, as a positive KRAS mutation is a predictor of a poor response to these drugs.

Patients with mutated or unknown KRAS status should receive chemotherapy including FOLFOX, CAPOX, or FOLFIRI with or without bevacizumab.

A small percentage of colorectal cancers have changes in one of the KRAS genes, which can cause abnormal cell growth and lead to cancer. KRAS is a member of the RAS family of genes that include NRAS and HRAS.

Receiving FDA approval in June 2024, Adagrasib (Krazati) is a drug that targets the KRAS protein and is approved to treat colorectal cancer that harbors a specific mutation (G12C). 

Other drugs targeting KRAS proteins are currently being tested in multiple clinical trials while some are approved for other cancer types and maybe available for off-label-use to treat colorectal cancer.  Be sure to ask your insurance provider if a drug is covered by your policy for off-label use.

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. 

What are the side effects of KRAS-targeted therapy drugs?

Possible side effects include nausea, vomiting, diarrhea, muscle and joint pain, fatigue, decreased appetite, and changes in liver and kidney function.

Talk to your care team about what you can expect when taking these drugs. Side effects that are more serious but rare include:

• abnormal heart function
• liver damage
• lung disease (interstitial lung disease)

Contact your doctor immediately if you are experiencing severe symptoms.