Lung Cancer

Molecular Testing & Biomarkers

Discovering the mutations (changes) present in cancer cells enables doctors to take a more patient-focused approach by offering access to treatments such as molecular therapy, targeted therapy or immunotherapy. These treatments are designed to target only the specific genetic abnormalities causing cancer and may spare you from aggressive treatments such as chemotherapy, which can damage healthy cells and result in many side effects. Molecular testing is the key to finding abnormalities in lung cancer, and this approach has revolutionized how lung cancer is treated today.

Cancer is a disease of our genes, which are pieces of DNA in our cells. Cancer forms when genes begin to change or mutate.

Several genes found in lung cancer may have mutations or fusions that contribute to cancer (see Table 1). A mutation is any change in the DNA sequence of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Fusions occur when two different genes are joined together. The result is a new gene that may lead to cancer.

Molecular testing is a broad term that refers to looking at a cancer’s biomarkers from biopsied tumor tissue or a blood sample (liquid biopsy). This testing is recommended specifically for non-small cell lung cancer (NSCLC), especially if the cancer is advanced. It is not typically used for small cell lung cancer (SCLC) diagnoses. Research is underway to determine whether SCLC may have mutations that can be targeted with therapy.

When Molecular Testing is Used

Also known as tumor profiling, molecular testing is performed in a laboratory to detect biomarkers, which are substances such as genes or molecules that can be measured in the blood, plasma, urine, cerebrospinal fluid or other body fluids or tissues. They are produced by cancer cells or other cells of the body in response to cancer.

For NSCLC, molecular testing is typically performed along with other tests before treatment begins to identify whether you are a candidate for molecular therapy, targeted therapy or immunotherapy. It may also be used during treatment to look for resistance to these therapies, or may be used if the cancer returns. When a tumor returns, it may have different genetic alterations than before, which may affect treatment options and prompt another round of biomarker testing.

Your doctor should order biomarker testing on a tissue sample collected during a biopsy and on a peripheral blood sample. Not all cancer centers offer molecular testing, but samples can be sent to a commercial lab, so it is important to ask whether it has been performed on your blood or tissue samples. Ask your doctor to explain which biomarkers were tested for and the results.

If the testing has not been performed, request it to find out whether you may have access to drug therapies that target the cancer. Knowing your lung cancer’s biomarkers will be crucial to the development of your treatment plan and will help you take a more active role in your care.

How Testing is Performed

The test(s) your doctor chooses may depend on the type of cancer you have and the known genetic alterations associated with it. Some cancer centers only test for one or two biomarkers, but comprehensive biomarker testing allows your doctor to look for all possible alterations regardless of whether drugs have been approved for them or not.

Tissue testing is most commonly used for these tests and frequently requires 2 to 3 weeks to obtain the final results. It may be difficult to wait for results, but it is valuable to determine whether you have any mutations for which therapy is available. A PD-L1 test can help determine whether immunotherapy is right for you and may provide results within 48 hours.

Blood sample results often come back within a week and are accurate enough for therapy selection. They are not as sensitive as tissue testing, so waiting for the tissue results is standard unless there is a need for immediate therapy.

In general, your doctor will follow these steps:

  1. A biopsy of tumor tissue is taken. It can be done by several methods, and different tests require different amounts of tissue.
  2. The sample is sent to a laboratory where a pathologist looks for the presence of cancer cells and documents certain characteristics of the tumor cells in the sample.
  3. Specialized equipment is used to sequence the tumor’s DNA and find any abnormalities.
  4. If abnormalities are found, they are compared to known mutations of the type or subtype of your particular cancer.
  5. Results are returned to your doctor in a pathology report.
  6. If testing finds a genetic alteration, your doctor may suggest options that are approved to target that alteration.
  7. If the genetic alteration found does not have a specialized treatment, your doctor may recommend standard of care treatment or a clinical trial that is testing the mutation identified in your tissue sample.

Talk with your doctor about when and how you will receive results.

Table 1.

Some Common Biomarkers In Lung Cancer

Description Type
Gene mutations BRAF
Gene fusions ALK
Biomarker for immunotherapy PD-L1
Optional biomarkers for immunotherapy Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR); tumor mutational burden (TMB)