Cancer Lung Cancer Non-Small Cell What Is KRAS G12C Mutation in Non-Small Cell Lung Cancer? By Heidi Moawad, MD Heidi Moawad, MD Facebook LinkedIn Heidi Moawad is a neurologist and expert in the field of brain health and neurological disorders. Dr. Moawad regularly writes and edits health and career content for medical books and publications. Learn about our editorial process Updated on May 07, 2023 Medically reviewed by Doru Paul, MD Medically reviewed by Doru Paul, MD Doru Paul, MD, is board-certified in internal medicine, medical oncology, and hematology. Learn about our Medical Expert Board Print Table of Contents View All Table of Contents Symptoms Causes Diagnosis Treatment The KRAS G12C mutation is the most common genetic abnormality associated with non-small cell lung cancer (NSCLC). The detection of this biomarker can provide insight into the prognosis of the disease, as well as its response to treatment. This mutation is believed to develop as a result of genetic alterations that occur in the body due to smoking. The KRAS G12C gene abnormality induces growth and proliferation of cancer. Research shows that having a KRAS G12C mutation with NSCLC is associated with a worse cancer prognosis and a reduced response to certain chemotherapeutic medications that are used for treating the disease. For some people who have NSCLC, identifying the KRAS G12C mutation helps guide cancer treatment. There are currently several potential treatments in development that inhibit the harmful activity of the KRAS G12C mutation. Verywell / Hugo Lin Symptoms Lung cancer can develop slowly, and it often doesn’t cause symptoms until the disease reaches late stages. Symptoms of advancing NSCLC can include weight loss, fatigue, shortness of breath, chest pain, coughing up blood, bone pain, and headaches. The symptoms of all types of lung cancer, including NSCLC, are more likely to develop as the cancer grows and invades the lungs or metastasizes (spreads to other areas of the body). For example, lung cancer can grow into the lung tissue, resulting in bloody sputum when you cough. Or it can spread to the bones, causing bone pain and increasing the risk of bone fractures. And cancer may increase the metabolic demands on the body, resulting in weight loss and generalized weakness. Symptoms of Non-Small Cell Lung Cancer Complications of KRAS G12C Lung Cancer Generally, NSCLC doesn’t cause substantially different symptoms than other types of lung cancer. And your cancer symptoms are unlikely to provide clues that you could have a KRAS G12C mutation. However, as the condition worsens, NSCLC associated with the KRAS G12 mutation can have a worse prognosis than some other lung cancer types. And this type of cancer does not typically improve with certain chemotherapeutic medications used for treating NSCLC. For example, the KRAS G12C mutation is a predictor that epidermal growth factor receptor (EGFR) mutations are absent and, therefore, tyrosine kinase inhibitors (TKI) targeting EGFR—which are approved in the treatment of NSCLC—will not be effective. These aren’t obvious clinical symptoms of the mutation, but they are complications of having the mutation. Causes Smoking, secondhand smoke, and inhaled toxins are the most commonly recognized causes of lung cancer. Most lung cancer, including adenocarcinoma of the lung and squamous cell carcinoma of the lung, are described as NSCLC. The cancer cells that grow in the lungs when a person has NSCLC are not the type of cell that is described as small cells, which is why it is called “non-small cell.” Causes and Risk Factors of Non-Small Cell Lung Cancer Oncogene There are a number of causes of NSCLC, and genetic changes in the cells are among the well-recognized causes. The KRAS gene is located on chromosome 12. It is an oncogene. An oncogene is a gene that can cause cancer to develop. A gene mutation is an alteration in the gene’s genetic code. When an oncogene’s genetic code is altered due to damage (such as the damage caused by smoking and other toxins), it can result in cancer. There are a number is different mutations that can occur in the KRAS gene, and the KRAS G12C mutation is a specific variation. It has been associated with several types of cancer. The most common cancer associated with the KRAS G12C mutation is NSCLC. The KRAS G12C genetic mutation is not inherited. It is believed to occur as a result of smoking. This type of chromosomal alteration leads to cancer because it results in abnormalities in the production of proteins that are directed by the KRAS G12C gene. The proteins that are altered by this particular mutation normally regulate cell growth, division, and survival. The specific protein irregularities caused by the mutation often lead to the type of abnormal cellular growth that is associated with cancer. Diagnosis and Testing Lung cancer is diagnosed with a combination of tests. Imaging tests of the chest, such as X-ray and computerized tomography (CT), can often identify cancerous growth in the lungs. Other tests, such as a bone scan or brain magnetic resonance (MRI) imaging tests, may identify metastasis. Often, these tests don’t distinguish between small cell lung cancer and NSCLC, and they can’t identify the KRAS G12C mutation. Biopsy A lung biopsy can differentiate NSCLC from other types based on the microscopic appearance of the cancer cells. If you have a biopsy, your healthcare providers will likely use a bronchoscopy procedure to obtain the sample of your lung tumor. A bronchoscope is a medical device that is placed into your lungs so your healthcare providers can see the tissue and take a biopsy sample. You would have some type of anesthesia during your procedure. If your medical team wants to determine whether you have a KRAS G12C mutation, a genetic test can be used to evaluate the cells obtained from your biopsy. In addition to identifying the cell type and the mutation, your NSCLC diagnosis includes an assessment of the cancer grade and stage. The grade is an evaluation of the aggressiveness of the cells and the likelihood of metastasis (based on their appearance under a microscope), while the stage describes the size of the cancer and how far it has spread. Treatment There are several treatment strategies used for lung cancer. Your treatment depends on a number of factors, such as the size of the tumor, the extent to which it has spread, and whether you have other medical conditions. Treatments include surgical removal of the tumor, chemotherapy, radiation therapy, and targeted therapy. In 2021, the Food and Drug Administration (FDA) approved Lumakras (sotorasib) for the treatment of NSCLC in those with the KRAS G12C mutation who have already received systemic therapy. In 2022, the FDA approved Krazati (adagrasib), the second targeted therapy for this mutation. Clinical Trials A number of clinical trials researching the effects of other KRAS G12C inhibitors for the treatment of NSCLC are currently taking place. The products being studied are described as covalent direct inhibitors that target KRAS G12C. The inhibitors bind to the mutated gene to have their anti-cancer effect. These KRAS G12C inhibitors work to inactivate the gene so that it will no longer continue to direct the production of cancer-causing proteins. Preliminary studies are promising, and several pharmaceutical companies are working on the development of possible drugs that could be available within upcoming years for people who have NSCLC with KRAS G12C mutations. How Non-Small Cell Lung Cancer Is Treated A Word From Verywell If you have been diagnosed with lung cancer, it can be frightening to think about your prognosis and treatment. You will need diagnostic testing to determine the type, stage, and grade of your cancer. Your treatment plan may include a number of approaches that can be used together to help optimize your outcome. If you have NSCLC with a KRAS G12C mutation, your treatment will be designed around the best management of this specific type of cancer. 7 Sources Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. Aredo JV, Padda SK, Kunder CA, et al. Impact of KRAS mutation subtype and concurrent pathogenic mutations on non-small cell lung cancer outcomes. Lung Cancer. 2019;133:144-150. doi:10.1016/j.lungcan.2019.05.015 Dogan S, Shen R, Ang DC, et al. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res. 2012;18(22):6169-77. doi:10.1158/1078-0432.CCR-11-3265 Fiala O, Pesek M, Finek J, Benesova L, Belsanova B, Minarik M. The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Cancer Genet. 2013;206(1-2):26-31. doi:10.1016/j.cancergen.2012.12.003 US National Library of Medicine. KRAS gene. Biernacka A, Tsongalis PD, Peterson JD, et al. The potential utility of re-mining results of somatic mutation testing: KRAS status in lung adenocarcinoma. Cancer Genet. 2016;209(5):195-198. doi:10.1016/j.cancergen.2016.03.001 U.S. Food and Drug Administration. FDA approves first targeted therapy for lung cancer mutation previously considered resistant to drug therapy. Seton-Rogers S. KRAS-G12C in the crosshairs. Nat Rev Cancer. 2020;20(1):3. doi:10.1038/s41568-019-0228-3 By Heidi Moawad, MD Heidi Moawad is a neurologist and expert in the field of brain health and neurological disorders. Dr. Moawad regularly writes and edits health and career content for medical books and publications. 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