Lung Cancer

Molecular Testing & Biomarkers

Dramatic progress is being made in the diagnosis and treatment of lung cancer due to the use of genetic/molecular testing. The results reveal specific information about the genes, proteins and other factors involved with your cancer. As a result, doctors are able to select therapies based on the tumor’s DNA. Depending on the genetic alteration your cancer has, a drug that is designed to target that abnormality may be available, providing you with a more personalized treatment plan.

Defining Molecular Testing

Typically performed along with other diagnostic tests before treatment begins, molecular testing uses samples of blood or tissue to identify a tumor’s genetic alterations, also called gene mutations or fusions (see Table 1). The results can indicate the cancer’s behavior in response to different drug treatments.

Blood and tumor tissue are examined to find possible genetic alterations in genes, chromosomes, proteins, enzymes or other molecules, and to look for biomarkers. Biomarkers are molecules produced or shed by cancer or other cells as a response to cancer. They are a sign that cancer is present.

This specialized testing also offers the possibility of treating lung cancer more effectively without damaging healthy cells, and may spare you from aggressive treatments that could have many side effects.

Benefits of Molecular Testing

This testing is recommended specifically for non-small cell lung cancer (NSCLC) patients – especially if the cancer is advanced – because starting treatment right away offers the best chance for a positive outcome.

Tissue testing is most commonly used for these tests and frequently requires 2 to 3 weeks to obtain the final results. Liquid biopsies are being used because of the ease and convenience of taking a blood sample versus a tissue sample and because results are available in a more rapid time frame (usually 7 days). Liquid biopsies are used to test for genetic alterations in DNA that is shed from the tumor.

The presence of certain mutations or biomarkers may make you eligible for molecular therapy, targeted therapy and immunotherapy.

Molecular testing may also be repeated during treatment for monitoring purposes and because cancer cells can evolve during treatment. If you become resistant to a treatment or have a recurrence, a new biopsy or liquid biopsy may be taken to check for new mutations.

Some cancer centers only test for one or two biomarkers, but comprehensive biomarker testing allows your doctor to look for all possible mutations regardless of whether drugs have been approved for that mutation. Now, next-generation sequencing of both DNA and RNA is the recommended standard.

Ask your Doctor About Testing

Not all cancer centers offer molecular testing, so it is important to determine 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 so that you have access to treatments that may target the cancer. 

Table 1.

Possible Biomarkers Tested for in Lung Cancer

Biomarker Description
Gene Mutations
BRAF A mutation that leads to uncontrolled cell growth and cancer. Tyrosine kinase inhibitors (TKIs) are only approved for the BRAF V600E mutation.
EGFR When mutated, EGFR drives abnormal cell growth so that the cancer grows unchecked. TKIs may be used as a first-line therapy.
ERBB2 (HER2) HER2 is a cell signaling receptor that is part of the EGFR family of receptors. A targeted therapy is approved and several others are being studied in clinical trials.
KRAS A mutation causes cells to grow without being instructed to. TKIs are approved for the specific mutation KRAS G12C and may be used as a first-line therapy. Other TKIs have not been approved for other types of KRAS mutations.
MET gene amplification (extra copies of the gene) and MET exon 14 skipping (promotes cell growth and cancer) have been identified in lung cancer. TKIs are only approved for MET exon 14 skipping mutations.
Gene Fusions
ALK A mutation in this gene is known as an ALK fusion or ALK rearrangement, and the cancer is considered ALK positive (ALK+). Tyrosine kinase inhibitors (TKIs) may be used as a first-line therapy.
NTRK When a fusion occurs, a piece of the NTRK gene and an unrelated gene join together and cause uncontrolled cell growth. TKIs may be used as a first-line therapy.
RET The main type of RET mutation in lung cancer is a RET rearrangement or gene fusion where a piece of DNA fuses with another gene. This leads to uncontrolled cell growth. TKIs may be used as a first-line therapy.
ROS1 When mutated, the ROS1 gene joins with part of another gene and causes uncontrolled growth. It may be known as a ROS1 fusion or ROS1 rearrangement. TKIs may be used as a first-line therapy.
Biomarkers for Immunotherapy
Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) Cancer cells that have large numbers of microsatellites may have defects in the ability to correct mistakes that occur when DNA is copied. Cancers with MSI-H and dMMR features appear to respond better to immunotherapy, though their presence is rare in lung cancer. When cancer cells have this feature, they are more sensitive to destruction by immune checkpoint inhibitors. This test is optional.
PD-L1 The amount of PD-L1 expression indicates whether you may benefit from immunotherapy with chemotherapy or immunotherapy alone. PD-L1 testing is mandatory in NSCLC only.
Tumor mutational burden (TMB) TMB is a measurement of the number of mutations in a tumor. Having more mutations may improve your chance of responding to immunotherapy. This test is optional.