Lung Cancer Genomic Testing (EGFR, KRAS, ALK)

Lung Cancer Genomic Testing (EGFR, KRAS, ALK)


In recent years, personalized medicine has begun to bring new hope to people with lung cancer, especially non-small cell lung cancer.

Personalized medicine involves looking at the cells obtained from a biopsy to see if there are any genetic mutations — changes in your genes — that could be linked to the type of cancer you have. For example, tumors in approximately 60 percent of patients with lung adenocarcinoma have been found to be linked to specific mutations.

Medical oncologist Marc Kris

Medical oncologist Marc Kris has been a key player in helping bring personalized medicine to people with lung cancer. He leads a research team working to find new genetic targets in cancer cells and to test anticancer medicines that specifically attack the lung cancers driven by these molecular changes.

Because certain chemotherapy drugs are either more or less effective than others against tumors with specific mutations, molecular analysis of your tumor, also called genomic testing, can help determine which therapies will be most likely to benefit you.

Genetic testing is now a routine part of diagnosis and staging for every patient we see with non-small cell lung cancer. We are one of only a handful of centers in the world to include this step. Based on which mutations we find, we may have a drug that has been approved for the changes in your specific tumor. Or you may be able to join a clinical trial that is testing a new drug.

Genetic information about your tumor can also help us predict the chances that your cancer will return after surgery and make other treatment decisions about surgery or radiation therapy.

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Testing for Specific Genetic Mutations

Samples from people with lung cancer at Memorial Sloan Kettering are routinely tested for all the major genetic mutations that are known to be important in the development of the disease. Our experts use a variety of technologies, including a new testing approach called MSK-IMPACT that screens for mutations in more than 300 genes at once.

Almost all of these genetic changes are found only in cancer cells, not in normal cells, which means they cannot be passed on to your children. The most common genetic changes that we test for in lung cancer are in the genes EGFR, KRAS, and ALK.

Testing for EGFR and KRAS Mutations

EGFR (the gene that produces a protein called epidermal growth factor receptor) is abnormal, or mutated, in about 10 percent of patients with non-small cell lung cancer and in nearly 50 percent of lung cancers arising in those who have never smoked.

Patients with cancer that has an EGFR mutation generally respond positively to treatment with the drug erlotinib (Tarceva®). If your tumor has an EGFR mutation, your doctor may recommend treatment with this drug or participation in a clinical trial.

Another mutation we regularly test for is in a gene called KRASKRAS is mutated in about 25 percent of patients with non-small cell lung cancer. If your tumor has a mutation in KRAS, your doctor may recommend a clinical trial specifically designed for patients with KRAS mutations.

Testing for Rearrangement of the ALK Gene

Patients whose tumors do not have mutations in either EGFR or KRAS may have another abnormality involving the ALK gene. This abnormality happens when ALK fuses to other genes, most commonly EML4. The result is a mutant gene called EML4-ALK, which changes the way the two fused genes function.

Nearly 5 percent of patients with non-small cell lung tumors and about 10 to 15 percent of people with non-small cell lung cancer who have never smoked have this abnormality.

If you’ve tested positive for EML4-ALK, you may benefit from the drug crizotinib (Xalkori®). Your doctor may also suggest you join a clinical trial of a new drug that targets this abnormality.

Testing for Squamous Cell Lung Cancer Mutations

More than 50 percent of patients with squamous cell cancer may have changes in proteins and molecular pathways.

Cancer cells that have these changes, which include alterations in the FGFR1 gene, the DDR2 gene, and the PI3K pathway, can be positively treated with novel therapies. We are looking for new personalized therapies for these mutations and may have a clinical trial you can join.

Testing for Small Cell Lung Cancer Mutations

Less is known about the mutations that cause small cell lung cancer. We are actively looking for mutations that can be used to guide treatment for small cell lung cancer patients.