What Is KRAS-Positive Lung Cancer?

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The Kirsten rat sarcoma viral oncogene homologue (KRAS) gene directs your body to make proteins that promote cell division and growth. Alterations in the KRAS gene are the most frequent mutations seen in non-small cell lung cancer, the most common type of lung cancer. KRAS mutations are not inherited, but acquired as a result of carcinogenic exposures.

KRAS-positive cancer is more difficult to treat than cancers that don't involve this mutation, but identifying it can help your doctor hone in on treatments that might work best for you.

What Being KRAS-Positive Means

The KRAS gene in your DNA contains the instructions for making the K-Ras protein.

This protein is part of RAS/MAPK, which is an important signaling pathway. The RAS/MAPK signals cells to grow and divide or to slow down their division. The K-Ras protein acts as a regulatory point in that pathway.

Having KRAS-positive lung cancer means that the KRAS gene in your DNA is damaged. This can occur from exposure to a carcinogen (a DNA-damaging agent) like tobacco smoke.

Due to this mutation, your cells might not be able to make normal K-Ras protein. Instead, they produce an altered protein that can't regulate the growth pathway as it should.

When the KRAS gene is acting abnormally like this, it’s called an oncogene. This might cause a person to develop a cancer—a group of cells that divide and grow more than is normal.

Several different KRAS mutations can lead to non-small cell lung cancer, and the most commonly identified of these is the KRAS-G12C, which is a mutation in a specific portion of the KRAS gene.

KRAS mutations are also sometimes found in other types of cancer, including pancreatic, colon, endometrial, bile duct, and small intestine cancers.

Other Important Lung Cancer Mutations

Mutations in other genes can also drive the growth of a cancer. In lung cancer, some of the other important driver mutations that can promote cancer growth are:

Usually, though not always, someone with a KRAS mutation in their tumor does not have an EGFR mutation or another major mutation driving the cancer.

Cancers with different genetic characteristics (e.g., KRAS-positive versus KRAS-negative) tend to respond differently to specific therapies. Most research has shown that people who are KRAS-positive tend to have cancer that is more difficult to treat successfully.

Who Develops KRAS Mutations?

Genetic mutations can be confusing. Some mutations are hereditary—they are inherited from parents and can cause or increase the risk of certain diseases. For example, the BRCA mutation is a hereditary mutation inherited from parents and it increases the risk of breast cancer and some other cancer types.

However, KRAS is not like this. It’s a mutation that you acquire and is prevalent in people who’ve smoked or who have been exposed to asbestos. It’s found only in the cancer cells and is believed to promote their growth.

In those of European descent, the KRAS mutation is found in about 30% of lung adenocarcinomas and in about 5% of lung squamous cell carcinoma (both subtypes of non-small cell lung cancer).

KRAS Testing

Knowing whether you have a KRAS mutation can help your doctors make the best treatment decisions for your lung cancer. The American Society of Oncology says that it may be helpful to check for mutations in KRAS and other genes if you have non-small cell lung cancer. For example, you may benefit from genetic testing if you have advanced lung adenocarcinoma.

Gene testing in lung cancer may also be helpful if you have another type of non-small cell lung cancer (with the exception of the squamous subtype), if you are under age 50, or have never smoked. It is not helpful for people with small cell lung cancers.

However, it’s not completely clear that KRAS testing provides additional helpful information if a person has already had positive genetic testing, like EGFR. This is still an evolving area of medicine.

People with metastatic colon cancer also sometimes benefit from KRAS testing, as it can also help guide therapy decisions.

As more targeted therapies become available for cancers with specific mutations, it has become critical to get this information.

How It's Done

Testing for the KRAS gene mutation will usually be done at the same time as other genetic cancer tests, like EGFR, BRAF, and ROS1. It might also be done after you’ve had some initial genetic tests for your cancer but haven’t yet found a driver mutation.

Usually, the KRAS test and other genetic tests are performed on a sample of the cancerous tissue itself. If you have already had surgery to remove your cancer, a sample might already be available. If not, a lung biopsy procedure is necessary. This might be done with the use of a long needle or obtained during bronchoscopy.

More recently, newer tests have become available that may be able to test for KRAS using a less invasive blood sample. Talk to your doctor about what options are available and appropriate for your particular situation.

Treatment

Researchers have developed targeted therapies for some of the genetic drivers of lung cancer. For example, therapies have been developed that work particularly well in people with ALK, EGFR, or ROS1 mutations.

Unfortunately, there are no such therapies specifically approved for treating KRAS-positive lung cancer. This marker is associated with a worse prognosis and lower response to standard chemotherapy.

KRAS-positive lung cancer doesn’t respond well to a group of drugs called tyrosine kinase inhibitors, which include Tagrisso (osimertinib). As such, your doctor might choose a different type of chemotherapy for you.

Your doctor may also recommend radiation, surgery, and supportive management.

Clinical Trials

Current research is looking for therapies that might be able to treat KRAS-positive lung cancers. For example, the KRAS G12C inhibitors AMG-510 and MRTX849 bind to the altered KRAS gene at a certain location—the G12C site—inactivating the gene.

This process stops the mutated gene from having its effect on cell growth, and it is considered a potential way to slow cancer growth. Both AMG-510 and MRTX849 are being studied as potential therapies alone and in combination with other cancer treatments. 

There are several ongoing investigations studying the effects of AMG-510, and there are approved human research trials investigating the effects of MRTX849 on patients who have KRAS-positive lung cancer as well.

Talk to your doctor if you might be interested in participating in a clinical trial for patients positive for the KRAS mutation. You can also check out clinicaltrials.gov to search for clinical trials being conducted around the world.

A Word From Verywell

Cancer diagnosis is advancing with tools that can specifically identify molecular features of different types of cancer. At the same time, cancer treatment is becoming more targeted and research focussed on cancer treatment for KRAS-positive lung cancer is underway.

Until targeted therapies become available, you can still get treatment for KRAS-positive lung cancer, potentially with a good outcome.

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  1. Domagala-Kulawik J. New frontiers for molecular pathologyFront Med (Lausanne). 2019;6:284. doi:10.3389/fmed.2019.00284

  2. Román M, Baraibar I, López I, et al. KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old targetMol Cancer. 2018;17(1):33. doi:10.1186/s12943-018-0789-x

  3. Kanwal M, Ding XJ, Cao Y. Familial risk for lung cancerOncol Lett. 2017;13(2):535–542. doi:10.3892/ol.2016.5518

  4. Tomasini P, Walia P, Labbe C, et al. Targeting the KRAS pathway in non-small cell lung cancerOncologist. 2016;21(12):1450–1460. doi:10.1634/theoncologist.2015-0084

  5. Kalemkerian GP, Narula N, Kennedy EB, et al. Molecular testing guideline for the selection of patients with lung cancer for treatment with targeted tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology clinical practice guideline update. J Clin Oncol. 2018;36(9):911-919. doi:10.1200/JCO.2017.76.7293

  6. Roberts PJ, Stinchcombe TE. KRAS mutation: should we test for it, and does it matter?. J Clin Oncol. 2013;31(8):1112-21. doi:10.1200/JCO.2012.43.0454

  7. Porru M, Pompili L, Caruso C, et al. Targeting KRAS in metastatic colorectal cancer: current strategies and emerging opportunitiesJ Exp Clin Cancer Res. 2018;37(1):57. doi:10.1186/s13046-018-0719-1

  8. Shen H, Che K, Cong L, et al. Diagnostic and prognostic value of blood samples for KRAS mutation identification in lung cancer: a meta-analysisOncotarget. 2017;8(22):36812–36823. doi:10.18632/oncotarget.15972

  9. Lam DC. Clinical testing for molecular targets for personalized treatment in lung cancer. Respirology. 2013;18(2):233-7. doi:10.1111/j.1440-1843.2012.02261.x

  10. Mccormick F. Sticking it to KRAS: Covalent Inhibitors Enter the Clinic. Cancer Cell. 2020;37(1):3-4.doi:10.1016/j.ccell.2019.12.009

  11. Nagasaka M, Li Y, Sukari A, Ou SI, Al-hallak MN, Azmi AS. KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne?. Cancer Treat Rev. 2020;84:101974.doi:10.1016/j.ctrv.2020.101974

  12. US National Library of Medicine.ClinicalTrials.gov. AMG-510. Updated May 13, 2020.

  13. US National Library of Medicine. Clinicaltrials.gov. MRTX849. Updated May 13, 2020.

  14. Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advancesTransl Lung Cancer Res. 2016;5(3):288–300. doi:10.21037/tlcr.2016.06.07