A mutation in the KRAS gene may affect your treatment options and outlook with colorectal cancer. Researchers are looking into new treatments that can target KRAS mutations.

Colorectal cancer occurs when healthy cells in the colon or rectum change and grow uncontrollably.

Colorectal cancer is the third most common cancer in men and women in the United States and the second most common cause of cancer deaths for men and women combined, according to the American Cancer Society.

When deciding on a treatment plan, your doctor will consider the stage of your colorectal cancer and your overall health, but there are other factors to consider. These include genetic mutations or biomarkers that may affect your risk and treatment options. Changes in the DNA of the tumor could be causing the tumor to grow, so targeting these changes directly could improve your outlook.

One genetic mutation known to increase the risk of colorectal cancer is the KRAS mutation. Around 45% of people with colorectal cancer have this particular gene mutation, per the National Cancer Institute. And research shows it’s linked to treatment resistance and worsened survival rates.

If you receive a colorectal cancer diagnosis, KRAS mutation testing may be necessary to help your doctor decide on the best treatment plan.

The KRAS gene instructs your body to make a protein that promotes regular cell growth and division.

A mutation is when a gene contains an error. When there is a mutation in KRAS, it tells your cells to grow too much, which causes cancer. A normal (unmutated) gene is called a wild-type gene.

KRAS, which stands for Kirsten rat sarcoma, is one of the most frequently mutated genes in colorectal cancer. Mutated versions of this gene are also linked to other cancer types, including lung and pancreatic cancer.

Why is KRAS so hard to target?

Over the years, researchers have found the KRAS protein particularly challenging to target for drug development. This is because the KRAS protein is small with a smooth surface, making it difficult for drugs to bind to it.

Because it’s so hard to target, the National Institutes of Health (NIH) has created the RAS Initiative to strengthen the effort toward targeting KRAS mutations.

Having a KRAS mutation may make someone with colorectal cancer more resistant to treatment with common cancer treatments called epidermal growth factor receptor (EGFR) inhibitors.

Therefore, if you have a KRAS mutation, you should not receive EGFR inhibitors like cetuximab (Erbitux) or panitumumab (Vectibix).

Your doctor may choose a different cancer treatment like chemotherapy or immunotherapy.

People with KRAS-mutated colorectal cancer have lower survival rates than those with a wild-type KRAS gene.

One small study conducted in Brunei, which included 76 people with metastatic colorectal cancer, found a significant difference between the outcomes of people with wild-type KRAS and those with mutant KRAS. In the study, the median survival of participants with mutant KRAS was 25 months, but 35 months for those with wild-type KRAS.

With new drugs in development targeting KRAS mutations, this outlook is likely to improve. The Food and Drug Administration (FDA) has approved two targeted therapies (sotorasib and adagrasib) for a specific subtype of KRAS-mutated, non-small cell lung cancer. The effectiveness of these therapies for colorectal cancer is still being evaluated.

The development of drugs targeting other subtypes is still at a relatively early stage.

The National Comprehensive Cancer Network now recommends KRAS mutation testing for anyone diagnosed with metastatic colorectal cancer.

Your doctor can confirm KRAS mutation with genetic testing. They’ll remove a small sample of your tumor (biopsy) and send it to a laboratory for testing.

At the laboratory, the sample is put through a specialized machine that can detect gene mutations like KRAS. This is called next-generation sequencing.

How common is the KRAS mutation in colorectal cancer?

About 45% of people with metastatic colorectal cancer have a KRAS mutation.

Is the KRAS mutation hereditary?

The KRAS mutation is not hereditary. KRAS mutations are somatic mutations, meaning the DNA changes occur after you’re born and can’t be passed on to your children.

What are the most common KRAS mutations in cancer?

There are many different KRAS mutations, known as variants or subtypes. Research suggests the most common KRAS variants in colorectal cancer are G12D, G12V, G12C, and G13D. In lung cancer, the most frequent KRAS variants are G12C, G12V, and G12D.

If you have colorectal cancer, knowing your KRAS mutation status can help guide your doctor toward a treatment plan that will likely work best to treat your cancer.

Currently, there are no specific anti-KRAS therapies for colorectal cancer, but research is ongoing. If you have metastatic colorectal cancer and tested positive for a KRAS mutation, talk with your doctor about the possibility of joining a clinical trial for a KRAS-targeted therapy.