Lung Cancer: Personalized Medicine

Pictured: Mark Kris Medical oncologist Mark Kris has helped lead efforts to bring lung cancer treatment into the age of personalized medicine.

In recent years, personalized medicine has become a very important part of treatment planning for people with non-small cell lung cancer. Because certain chemotherapy drugs are either more or less effective than others against tumors with certain mutations, molecular analysis of your tumor can help to determine which therapies will be most likely to benefit you.

Our pathologists have the ability to test your tumor for genetic mutations that we now know are closely linked to specific types of non-small cell lung cancer. Tumors in approximately 60 percent of patients with lung adenocarcinoma have been found to be linked to specific mutations. For some of these mutations, drugs approved by the US Food and Drug Administration are available. In others, experimental treatments being tested in clinical trials may be the best option.

Information about the genetics of a tumor can also help to predict the chances of cancer returning after surgery. And if a cancer has come back or cannot be cured with an operation or radiation therapy, knowing about these mutations can help your doctors to plan other treatments to shrink the tumor.

Advancing Personalized Medicine at Memorial Sloan Kettering

Memorial Sloan Kettering Cancer Center was one of the first centers to apply this new approach to cancer treatment. Our pathologists now include genetic testing of the tumor as a routine part of the diagnosis and staging procedure for all men and women treated for non-small cell lung cancer. We are one of only a handful of centers in the world to do so.

Our pathologists analyze cells in your tissue sample to look for genetic mutations that are found only in the cells of certain subtypes of lung cancer. The tissue is usually obtained during the biopsy that is performed to determine which type of lung cancer you have. Sometimes there may not be enough tissue left to perform the genetic testing, in which case you may be asked to have another biopsy.

Before we perform any tests, we will ask your permission to look for mutations that could help your doctor tell you whether a clinical trial of an experimental treatment might be an option for you. 

Analyzing Tumors for Genetic Mutations

Samples from patients with lung cancer at Memorial Sloan Kettering are routinely tested for all the major genetic mutations that are known to be clinically important in lung cancer. Our experts use a variety of technologies, including, as of January 2014, a new testing approach called MSK-IMPACT that screens for mutations in over 300 genes at once.

Almost all of these genetic changes (called somatic mutations) are found only in cancer cells, not in your normal cells, and 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 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 whose cancer is found to have 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 erlotinib or participation in a clinical trial.

Another mutation we regularly test for is in a gene called KRAS. KRAS is found to be abnormal, or 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 in which a gene called ALK is fused to other genes, most commonly EML4. The result is a mutant gene called EML4-ALK, which occurs when the two genes fuse into a hybrid form that changes the way the two genes function.

This abnormality, found in nearly 5 percent of patients with non-small cell lung tumors, is present in about 10 to 15 percent of people with non-small cell lung cancer who have never smoked. 

Patients whose tumors have EML4-ALK may benefit from the drug crizotinib (Xalkori®), and may also be eligible for clinical trials of new drugs that target this abnormality.

Testing for BRAF Mutations

We are able to identify mutations in the gene BRAF in about 3 percent of people with lung adenocarcinoma. This mutation mostly occurs in patients who are either smokers, or who were smokers in the past.

Preliminary research has already shown that some drugs can block the effects of mutated BRAF genes in people with melanoma, an aggressive form of skin cancer. Memorial Sloan Kettering is conducting clinical trials to test whether a similar strategy might be effective for non-small cell lung cancer.

Testing for Squamous Cell Lung Cancer Mutations

Research has identified changes in proteins and molecular pathways in more than 50 percent of patients with squamous cell cancer. 

Cancer cells that have these changes, which include alterations in the FGFR1 gene, DDR2 gene, and PI3K pathway, can be positively treated with novel therapies. We are conducting clinical trials for patients whose squamous cell lung cancers have these molecular changes, with the hope of identifying new, tailored therapies.

Testing for Small Cell Lung Cancer Mutations

Less is known about the critical mutations that cause small cell lung cancer. We have initiated a similar approach to characterize and classify small cell lung cancers based on mutations found in the tumors. This approach, which is offered in the form of a clinical trial, may identify mutations that can be used to guide therapy for small cell lung cancer patients as well.