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 — treating patients with drugs and other therapies that are tailored to the exact genetic changes present in their tumor cells — has started to become a reality for patients with certain types of cancer, including many patients with lung cancer. Researchers now have the ability to test patients' tumor samples for the presence of genetic mutations that are linked to lung cancer and — in many cases — to offer drugs that are targeted to those particular mutations.
Memorial Sloan-Kettering Cancer Center was one of the first centers to apply this new molecular approach to cancer treatment. Our pathologists now include genetic testing 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 small 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 in January 2009.
As they review tissue samples, pathologists look for genetic mutations that are known to play a role in non-small cell lung cancer and to affect how the cancer responds to various therapies. Following removal of a tumor by surgery, this information can help predict the chances of the cancer coming back and determine the options for chemotherapy. If the cancer has come back or the cancer cannot be cured with an operation or radiation, knowing about these mutations will help doctors figure out which treatments are more likely to help shrink the cancer.
EGFR and KRAS
One genetic mutation that we regularly test for is in a gene called EGFR. EGFR, or 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®). Knowing which patients have EGFR mutations allows doctors to determine who will benefit from treatment with this drug. If patients do not have an EGFR mutation, they can then be given more appropriate and efficacious treatment for their disease.
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. When a patient's lung cancer is found to have a mutation in KRAS, the team caring for that patient will have more information about the cancer, enabling treatment decisions to be made more easily.
Also, we have developed an infrastructure of clinical trials specifically for patients whose tumors have KRAS mutations. Knowing about KRAS mutations will allow your doctor to suggest clinical trials that are right for you.
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) that ordinarily work fine on their own 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. If a tumor has an EGFR or KRAS mutation, then it will not have EML4-ALK. Patients whose tumors have EML4-ALK may be eligible for a clinical trial of new drugs that target this abnormality.
In addition to mutations in the EGFR and KRAS genes as well as EML4-ALK, Memorial Sloan-Kettering tests patients' tumors for the expression of certain cell proteins. Patients with these proteins in their tumors may be less likely to benefit from traditional chemotherapy given after initial treatment (known as adjuvant chemotherapy).
In total, we test for more than 40 mutations in more than 7 genes that are known to occur in lung cancer.
Testing done by the LC-MAP program may also direct patients into clinical trials designed for individuals whose cancer has recurred after initial treatment. These trials are investigating the use of drugs that are already being used as standard treatment for other cancers, as well as new agents, including targeted therapies and vaccines.
| Test | Effects on a Patient's Treatment |
|---|---|
| EGFR mutation test |
Patients with this mutation in their tumor may be eligible for a clinical trial of a new drug that targets the EGFR, or the doctor they see may recommend using erlotinib, an FDA-approved treatment, rather than regular chemotherapy. |
| EML4/ALK |
Patients with this mutation in their tumor may be eligible for a clinical trial of a new drug that targets the ALK protein. |
|
KRAS mutation test |
Patients with this mutation in their tumor may be eligible for a clinical trial of a vaccine against mutant KRAS protein or trials of other drugs, depending on what stage cancer they have. |
|
BRAF |
Patients with this mutation, which is identified as part of our LC-MAP program, may be eligible for clinical trials of drugs that target this pathway. |
Clinical Trials
Many patients whose cancer recurs following standard treatment will be offered the opportunity to participate in clinical trials that may benefit them based on the molecular makeup of their individual tumors. Some of these trials are investigating new uses of drugs that are already part of standard treatment for other types of cancer, whereas other studies are evaluating new agents, including targeted therapies and vaccines.
Having this extensive information about the molecular details of our patients' tumors can help guide the team of doctors in treatment decisions. It also allows us to direct patients toward clinical trials that are most likely to be effective against their individual cancer types.
