Lung cancer biomarkers are pieces of DNA, proteins, or hormones that cancer cells release, or that your body releases in response to cancer.

Your doctor can test for these markers in your:

  • blood
  • urine
  • stool
  • tissues
  • other bodily fluids

In the past, everyone with lung cancer got the same treatment. Now there are targeted treatments based on biomarkers.

More than 1 in 4 people with adenocarcinoma, a type of non-small cell lung cancer (NSCLC), have a biomarker with a targeted treatment.

Your doctor can also use biomarkers to diagnose your cancer and find out how quickly it might grow.

Biomarkers help predict which treatment is most likely to work best against your cancer. Biomarkers can also show how well your treatment is working.

There are two main types of lung cancer biomarkers:

  • gene changes (mutations) or rearrangements that promote the growth of cancer cells
  • immune system biomarkers that predict how well your cancer will respond to immunotherapy

Gene mutation biomarkers include:

  • EGFR. It leads to the production of a protein that makes cancer cells grow too much. Between 10 and 15 percent of lung cancers test positive for EGFR.
  • ALK. It can get fused to another gene or moved from its normal position. About 4 percent of lung cancers are ALK positive.
  • BRAF V600E. This mutation leads to the production of an abnormal protein, also called BRAF, that makes cancer cells grow too much. About 4 percent of NSCLCs are BRAF mutations.
  • MET. This gene codes for the MET protein, which sends growth signals to the cancer. A mistake called exon 14 skipping prevents the MET protein from being broken down, leading to more of it in your body. About 5 percent of people with lung cancer have MET 14 skipping.
  • PIK3. It affects a protein that’s important to the growth and survival of lung cancer cells. PIK3 mutations affect up to 4 percent of people with NSCLC.
  • HER2. This gene mutation sends signals to fuel the cancer’s growth. The same gene mutations are involved in breast and ovarian cancers. About 3 percent of lung cancers test positive for HER2.
  • ROS1. This gene can be in the wrong place or fused to part of another gene. ROS1 is mutated in 1 to 2 percent of people with lung cancer.
  • RET. It can be in the wrong place or fused to another gene. About 1 to 2 percent of people with lung cancer have a RET gene change.
  • NTRK. It can become fused to another gene, leading to uncontrolled cell growth. Less than 1 percent of lung cancers have this gene change.

Immune system markers for lung cancer include:

  • PD-1 and PD-L1. These proteins are found on the surface of healthy cells and in larger amounts on some cancer cells. They act like a “brake” to stop the immune system from attacking the cancer.
  • CTLA-4. This protein also impedes the immune response against cancer.

Biomarker testing, also called molecular and genetic testing, gives your doctor more information about your tumor. These tests are recommended for everyone who receives a NSCLC diagnosis.

Your doctor will take a small piece of your tissue or blood for testing. The sample goes to a laboratory or testing company to check for DNA mutations and levels of certain proteins.

There are a few ways to detect lung cancer biomarkers:

  • Comprehensive next-generation sequencing (NGS) runs a piece of your tissue through a machine to look for many biomarkers at the same time.
  • FISH analysis uses a special fluorescent dye to find cancer genes.
  • Immunohistochemistry uses proteins called antibodies to locate markers in the tissue sample.
  • Liquid biopsy looks for cancer DNA in a sample of your blood.
  • PD-L1 testing measures the percentage of cells in a tumor that express the protein PD-L1.

Biomarker tests find DNA changes and proteins that are specific to your tumor. Your doctor will get a report that shows which biomarkers are in your cancer or blood.

Biomarkers can help point your doctor to the targeted treatment or immunotherapy that’s most likely to work against your cancer. The Food and Drug Administration (FDA) has approved treatments for many biomarkers, including:

  • EGFR
  • ALK
  • ROS1
  • BRAF
  • PD-L1
  • RET

Biomarker research took off in the early 2000s with the approval of the first drugs targeting EGFR-positive lung cancer. Since then, researchers have discovered more than 20 different driver mutations that contribute to lung cancer development.

Eight drivers have drugs approved to treat them, but these medications don’t work in people without gene changes.

The search is on for more biomarkers, which will hopefully lead to new targeted lung cancer treatments.

The FDA has approved more than 20 targeted therapies for people with specific lung cancer biomarkers.

EGFR-positive lung cancers are treated with a group of drugs called tyrosine kinase inhibitors (TKIs):

  • afatinib (Gilotrif)
  • dacomitinib (Vizimpro)
  • erlotinib (Tarceva)
  • gefitinib (Iressa)
  • osimertinib (Tagrisso)

ALK-positive lung cancers are treated with ALK inhibitors:

  • alectinib (Alecensa)
  • brigatinib (Alunbrig)
  • ceritinib (Zykadia)
  • crizotinib (Xalkori)
  • lorlatinib (Lorbrena)

BRAF-positive lung cancer treatment involves a combination of two drugs:

  • dabrafenib (Tafinlar)
  • trametinib (Mekinist)

MET exon 14 skipping lung cancer has only one approved treatment:

  • capmatinib (Tabrecta)

ROS1-positive lung cancers are treated with these medications:

  • crizotinib (Xalkori)
  • entrectinib (Rozlytrek)

RET rearrangements are treated with drugs called RET inhibitors:

  • pralsetinib (Gavreto)
  • selpercatinib (Retevmo)

NTRK gene fusions have two approved targeted therapies:

  • entrectinib (Rozlytrek)
  • larotrectinib (Vitrakvi)

Immunotherapy drugs for NSCLC block the proteins PD-1 or PD-L1:

  • PD-1 inhibitors include nivolumab (Opdivo) and pembrolizumab (Keytruda).
  • PD-L1 inhibitors include atezolizumab (Tecentriq) and durvalumab (Imfinzi).

Biomarkers have improved the diagnosis and treatment of lung cancer. These gene changes have led to new and more precise treatments. If you have a lung cancer diagnosis, ask your doctor whether you should have biomarker or molecular testing.

If you don’t test positive for a biomarker that has a matching treatment, find out if you can enroll in a clinical trial.

These studies are testing many other possible lung cancer treatments. You might qualify to try a drug that hasn’t yet been approved.