This test detects specific mutations in the KRAS gene in the DNA of cancer cells and tissue. The presence of these mutations may indicate that certain drugs will not be effective in treating the cancer.
KRAS is a short name for the gene Kirsten rat sarcoma viral oncogene homolog. It is one of a group of genes involved in a pathway called the epidermal growth factor receptor (EGFR) pathway. This complex signaling pathway involves numerous components that relay signals from outside of the cell to within the cell to help regulate cell growth, division, survival and death.
In many normal cells, binding of epidermal growth factor (EGF) to its receptor (EGFR) on the surface of the cell is an important signal for cell growth and division. Other signals in the pathway involve a class of proteins called tyrosine kinase (TK) enzymes and a protein produced by the KRAS gene. Normally, the components of the pathway interact in the regulation of cell growth and division and do not individually stimulate cell proliferation.
However, in some cancers, EGFR becomes active even in the absence of EGF, leading to uncontrolled cell growth and division. Drugs that inhibit EGFR or tyrosine kinase enzymes are often helpful for treating such cancers. Some of these cancers, though, have a mutation in the KRAS gene that produces an abnormal K-Ras protein. The abnormal protein is always active and can stimulate cell growth even in the absence of signals from EGFR or other tyrosine kindase proteins. In such cancers, drugs that inhibit EGFR or tyrosine kinases will not be effective.
KRAS is mutated in 15% to 20% of human cancers, mostly in pancreatic cancer, colon cancer and lung cancers as well as leukemias. Approximately 30% to 40% of colon cancers and 15% to 30% of lung cancers have KRAS mutations. Currently, drugs that target EGFR are used to treat colon cancer and non-small cell lung cancer. KRAS mutation testing is used to determine whether these drugs will be effective in treating these cancers.
There are several different methods of testing for KRAS mutations, but all of them involve evaluating the KRAS gene in tumor tissue.
How is the test used?
This test detects the presence of the most common KRAS gene mutations in the DNA of cells in tumor tissue in order to help guide cancer treatment. KRAS mutation analysis is ordered primarily to determine if your metastatic colon cancer or non-small cell lung cancer is likely to respond to standard therapy, an anti-EGFR drug therapy. Tumors with the KRAS mutation do not respond to anti-EGFR therapy.
If your tumor is negative for the most common KRAS mutation, tests for other less common mutations not detected by the current test may be used to help predict therapeutic responses.
When is it ordered?
What does the test result mean?
If tissue from your cancer contains a KRAS mutation, then you will not benefit from EGFR targeted therapies. The presence of a KRAS mutation also indicates a likely poorer prognosis, although the presence of a specific mutation cannot predict how severe or aggressive the cancer will be.
A negative result on the KRAS test indicates that your cancer may respond to anti-EGFR therapy, but the lack of a KRAS mutation as determined by the KRAS test does not ensure this. A negative test could occur when the tumor tissue sample is insufficient or when some of the cancer cells in the tumor contain the mutation and others do not. Additionally, there may be KRAS mutations that are not detected by some tests because of their particular location in the DNA. Other factors may also lead to cancer that is resistant to anti-EGFR drugs.
Is there anything else I should know?
Guidelines from both the American Society of Clinical Oncology and the National Comprehensive Cancer Network have recommended KRAS mutation testing prior to anti-EGFR therapy.
Current anti-EGFR drug therapies include:
- For colon cancer, anti-EGFR monoclonal antibodies such as cetuximab and panitumumab that block binding of receptors
- For non-small cell lung cancer, anti-EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib that prevent activation of signaling pathways
Should everyone with cancer have KRAS mutation testing?
Would this testing and drug therapy be useful for other types of cancer?
It is possible, since KRAS mutations are found in other cancers. This is a focus for medical researchers, but it may be some time before the usefulness of the testing and therapy in other cancers is determined. For example, whether KRAS mutations are associated with less efficient EGFR-targeted therapy in pancreatic cancer patients remains controversial and requires further investigation.
Is it necessary to repeat a KRAS mutation test?
This is not usually necessary but might occur if your health practitioner thought that the first sample tested might have been insufficient. In some cases, a health care provider may order a KRAS test that detects a mutation in another part of the DNA or another more rare KRAS mutation. Sometimes metastatic tumors may be not be accessible or have limited tissue for testing. In these cases, a sample (if available) from your primary cancer may be obtained for testing. Frequently, if the primary tumor has a KRAS mutation, so will the metastatic tumor.
Can this test be performed by my local laboratory?
Can this test be performed on my blood instead?