Mark Kris is chief of Memorial Sloan-Kettering's Thoracic Oncology Service. He has helped lead efforts to bring lung cancer treatment into the age of personalized medicine.
In recent years, the idea of personalized medicine has become a reality for people with non-small cell lung cancer.
Doctors at Memorial Sloan-Kettering 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.
Because certain chemotherapy drugs are more effective than others against tumors with specific mutations, genetic testing of your tumor can help to determine which therapies will be most likely to be of benefit to you. For some of these mutations, an FDA-approved drug is available. In others, a clinical trial of a new, experimental treatment is 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 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.
Genetic testing of lung cancer tumors is conducted as part of the Lung Cancer Mutation Analysis Project (LC-MAP), which began at Memorial Sloan-Kettering in January 2009, and the Squamous Cell Lung Cancer Mutation Analysis Project (SQ-MAP), which began in October 2011.
In total, we test for more than 90 genetic mutations that are known to occur in lung cancer. These genetic changes (called somatic mutations) are found only in cancer cells, not in your normal cells. They cannot be passed on to your children.
The most common mutations that we test for are in the genes EGFR and KRAS, and the EML4-ALK fusion gene. Memorial Sloan-Kettering also tests non-small cell lung tumors for the expression of certain cell proteins. Patients with these proteins in their tumors may be less likely to benefit from chemotherapy either before or after surgery.
EGFR and KRAS
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. If not, you can then receive a more appropriate treatment.
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.
EML4-ALK
Patients whose tumors do not have mutations in either EGFR or KRAS may have another abnormality called an EML4-ALK fusion gene. This is a mutant gene that occurs when two genes (EML4 and ALK) become fused into a hybrid form that changes the way they 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 never smoked.
Patients whose tumors have EML4-ALK may be eligible for a clinical trial of new drugs that target this abnormality.
BRAF
The LC-MAP program identified 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.
The protein that is produced by BRAF is a part of a molecular pathway that transmits signals from the surface of a cell to its interior. In cancer cells, this pathway can cause cells to divide and cancer to progress. Researchers hope that by blocking this pathway, it might be possible to slow the spread of cancer.
Preliminary research has already showed 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.
Squamous Cell Lung Cancer Mutation Analysis Project (SQ-MAP)
With the launch of the SQ-MAP program in October 2011, we have now expanded our routine genetic testing program to include tumors from patients with squamous cell lung cancers. Research has identified changes in proteins and molecular pathways that can be found in more than 50 percent of patients with this disease.
Cancer cells that have these changes, which include alterations in the FGFR1 gene, DDR2 gene, and PI3K pathway, can be positively treated with experimental drugs. We are conducting clinical trials for patients whose squamous cell lung cancers have these changes, with the hope of identifying new, tailored therapies.
Our Clinical Trials
Memorial Sloan-Kettering is conducting a number of clinical trials to test the effectiveness of this molecular approach in personalized medicine. If the molecular makeup of your tumor matches certain eligibility criteria, your doctor may offer you the opportunity to participate in a clinical trial. Participating in a clinical trial may give you access to treatments that are not widely available, and may offer additional options if your cancer has returned after standard treatment. It’s also a way to make a contribution in the fight against cancer.
Learn more about our clinical trials.
