The KRAS gene provides instructions for making a protein that regulates cell growth and division. When this gene undergoes a specific alteration, known as the G12C mutation, it can disrupt normal cellular processes. This mutation is a focus in oncology because it is found in non-small cell lung cancer (NSCLC). Identifying the KRAS G12C mutation through genetic testing allows oncologists to understand the specific drivers of a patient’s cancer, which helps guide the selection of therapies tailored to the tumor’s unique genetic profile.
The Role of KRAS G12C in Cancer
The KRAS protein functions like a switch, cycling between “on” and “off” states to control cell division. The G12C mutation, however, causes this switch to become permanently stuck in the “on” position. This malfunction leads to a constant signal for the cells to grow and divide without stopping.
This uncontrolled proliferation of cells is a hallmark of cancer development, leading to the formation of tumors. The KRAS G12C mutation is not found in all cancers but is particularly common in specific types. It is one of the most prevalent mutations in non-small cell lung cancer, occurring in about one out of every eight patients with this diagnosis. Beyond the lungs, this mutation is also frequently identified in colorectal and pancreatic cancers.
The Genetic Testing Process
To determine if a tumor harbors the KRAS G12C mutation, specialists perform genetic testing on the cancer cells. The most established method is a tissue biopsy, which involves the surgical removal of a small piece of the tumor. This sample is then sent to a pathology lab where its genetic material is analyzed to look for the G12C mutation among other potential biomarkers.
A less invasive alternative is the liquid biopsy, a blood test. This technique works by detecting and analyzing circulating tumor DNA (ctDNA), which are tiny fragments of genetic material that tumors shed into the bloodstream. A liquid biopsy can be particularly useful when a tissue biopsy is not feasible due to the tumor’s location or if the patient is not well enough for the procedure.
These tests are examples of somatic testing, meaning they analyze the genes of the cancer cells themselves. This is different from germline testing, which looks for hereditary mutations that are passed down through families. The KRAS G12C mutation is typically an acquired change within the tumor and not an inherited trait.
Understanding Test Results
The report from a KRAS G12C genetic test provides clear, actionable information. A “positive” result indicates that the G12C mutation has been detected within the DNA of the patient’s cancer cells. This finding confirms that the KRAS protein is a contributing factor to the tumor’s growth and provides a specific molecular target for treatment.
Conversely, a “negative” or “wild-type” result means that the KRAS G12C mutation was not found in the tumor sample that was tested. This outcome does not alter the underlying cancer diagnosis. It simply signifies that the cancer’s growth is driven by different genetic mutations, which directs the medical team to explore other treatment pathways.
Treatment Implications of a Positive Result
Discovering a KRAS G12C mutation opens the door to a specialized approach called targeted therapy. These are medications engineered to attack cancer cells that have specific genetic alterations, while largely sparing normal, healthy cells. For patients with a positive test result, this means they may be eligible for a class of drugs known as KRAS G12C inhibitors. The U.S. Food and Drug Administration (FDA) has approved specific drugs in this class for treating patients with this mutation.
These inhibitor drugs work with high precision. They are designed to fit into a specific pocket on the mutated KRAS G12C protein, effectively blocking its activity. By doing so, they turn off the constant “on” signal that drives uncontrolled cell growth, which can lead to a reduction in tumor size and a slowing of cancer progression.
Targeted therapies like KRAS G12C inhibitors are often incorporated into a patient’s treatment plan after they have already undergone initial treatments, such as chemotherapy. For instance, they are approved for adult patients with NSCLC that has spread and who have received at least one prior systemic therapy. The field is continuously advancing, with numerous clinical trials underway to investigate new KRAS inhibitors and explore their use in combination with other cancer treatments to improve patient outcomes.