The RAS gene family is a heavily studied group of genes. They include KRAS, NRAS, and HRAS. KRAS and NRAS are most commonly found in GI cancers, with KRAS being the most common mutated gene in the family.
Within each of these genes, mutations can occur in specific areas. For example, a KRAS mutation can be a specific variant called G12C or G12D. Researchers are discovering ways to reach these specifically mutated areas with targeted therapy.
Each of the RAS genes make a protein that works like a hall monitor for cells that are growing, dividing, and moving throughout a certain “hallway” (called the RAS/MAPK pathway). These proteins are also sending reports from the surface of a cell to the center (the nucleus) and telling the cell what to do and how to behave.
When the genes are acting normally, the protein is working in healthy shifts as it monitors cells growing and dividing. It goes on and then it goes off. This is called “wild-type” (WT) or normal.
Sometimes, after birth, a mutation in a RAS gene can form. This is not typically caused by an inherited condition. Many circumstances can cause a gene to mutate, like problems that occur when a cell divides or external factors. When the gene mutates, the protein it creates stops taking breaks and is constantly working.
This can lead to cells growing and dividing uncontrollably, causing chaos in the “hallway.” In this environment, an (often aggressive) cancer grows. This is called “mutant” or positive.
Biomarker testing can be run on tumor or blood samples to determine if there’s a mutation in a RAS gene. If so, there are a few implications.
Tumors that are RAS-mutant (For example, KRAS-mutant) generally do not respond to anti-EGFR therapies like panitumumab (Vectibix) or cetuximab (Erbitux). These drugs are prescribed for RAS wild-type (not mutated) tumors.
There are a few targeted therapies available for treatment: a set of drugs called “inhibitors.”
Colorectal cancers (in advanced, specific situations - KRAS G12C mutations only)
Clinical trials are currently underway for patients with other common RAS mutations across several GI cancer types. RAS mutations under investigation include KRAS G12D, G12V, and others.
Each treatment plan depends on your stage, line of treatment, surgical or additional treatment options, and your overall health.
Your treatment plan will be unique and dependent on several factors. Ask your doctor how your biomarker test results are informing your treatment plan and if you qualify for any clinical trials.
