Lung cancer biomarkers are types of proteins, hormones, or pieces of DNA. They play a role in diagnosis and treatment. Targeted therapies and immunotherapy drugs are available for certain biomarkers.
Lung cancer biomarkers are proteins, hormones, or pieces of DNA that cancer cells release, or that your body releases, in response to cancer.
A doctor or another type of healthcare professional can test for these biomarkers in your:
- other bodily fluids
In the past, everyone with lung cancer got the same treatment. Now there are targeted treatments based on biomarkers.
Biomarkers help predict which treatment is most likely to work best against your cancer. Biomarkers can also show how well your treatment is working.
A doctor can also use biomarkers to diagnose your cancer and find out how quickly it might grow.
While biomarkers do exist for small-cell lung cancer, biomarkers are primarily used in the diagnosis and treatment of non-small cell lung cancer (NSCLC).
There are two main types of lung cancer biomarkers:
- Mutations: Mutations are gene changes or rearrangements that promote the growth of cancer cells.
- Immune response biomarkers: These biomarkers predict how well your cancer will respond to immunotherapy.
Gene mutation biomarkers for NSCLC include:
- Tumor protein p53 (TP53): TP53 is the most common mutation in NSCLC. It’s found in around 50% of people with NSCLC.
- KRAS: KRAS is the second most common mutation in NSCLC. About 30% of people with NSCLC have the KRAS mutation. A mutation known as the serine/threonine kinase 11 (STK11) mutation often appears alongside it.
- Epidermal growth factor receptor (EGFR): The EGFR mutation leads to the production of the EGFR protein, which makes cancer cells grow too much. Around 10% to 15% of lung cancers in the United States test positive for EGFR. There are multiple subtypes of EGFR mutations, with EGFR exon 19 deletion and EGFR exon 21 L858R point mutations being the most common. Learn more about EGFR-positive lung cancer.
- Anaplastic lymphoma kinase (ALK): The ALK gene can get moved from its normal position or fused to another gene, such as the echinoderm microtubule-associated protein-like 4 (EML4) gene.
About 5%of people with NSCLC have ALK-positive lung cancer.
- Mesenchymal-epithelial transition (MET) and MET exon 14 (METex14): The MET gene codes for the MET protein, which sends growth signals to your cancer. An error called exon 14 skipping prevents the breakdown of a specific type of the MET protein. This leads to more of the protein in your body.
Up to 5%of people with NSCLC have the MET mutation. The METex14 mutation is involved in the cancers of about 3% of people with NSCLC.
- Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA): The PIK3CA mutation affects the p110 alpha protein. This protein is important to the growth and survival of lung cancer cells. PIK3CA mutations affect under 5% of people with NSCLC.
- BRAF: This mutation leads to the production of an abnormal protein that makes cancer cells grow too much. Up to 3.5% to 4% of people with NSCLC have BRAF mutations. Half of those people have the BRAF V600E mutation, the most common subtype of the BRAF mutation.
- Human epidermal growth factor receptor 2 (HER2): The HER2 gene mutation sends signals to fuel your cancer’s growth. HER2 gene mutations are also involved in breast and ovarian cancers. Between 1% and 4% of people with NSCLC have HER2 gene mutations.
- ROS1: This gene can be in the wrong place or fused to part of another gene. ROS1 is mutated in 1% to 2% of people with NSCLC.
- RET: The RET gene can be in the wrong place or fused to another gene. Between 1% to 2% of people with NSCLC have this mutation.
- Neurotrophic tyrosine receptor kinase (NTRK): The NTRK gene can become fused to another gene, leading to uncontrolled cell growth. Around 1% of people with NSCLC have this gene change.
- NRAS: NRAS is a rare biomarker for lung cancer, affecting under 1% of people with NSCLC.
Immune response biomarkers for NSCLC include:
- Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1): These proteins are located on the surface of healthy white blood cells known as T cells. They’re also located in larger amounts on some cancer cells. They act like a “brake” to stop your immune system from attacking the cancer.
- Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4): This protein is also located on the T cells. It impedes your immune response against cancer.
Biomarker testing gives a doctor more information about your tumor. These tests are recommended for everyone who receives a diagnosis of NSCLC.
A doctor will take a small sample of your tissue or blood. The sample goes to a laboratory or testing company where it’s checked for DNA mutations and levels of certain proteins.
There are a few ways to find lung cancer biomarkers:
- Next-generation sequencing (NGS): In comprehensive NGS, a piece of your tissue or a blood sample is run through a machine, which can reveal multiple biomarkers at once.
- Fluorescence in situ hybridization (FISH): The FISH technique uses a special fluorescent dye to find cancer genes.
- Immunohistochemistry: Immunohistochemistry is a staining technique that uses proteins called antibodies to locate biomarkers in a tissue sample.
Learn more about genetic testing, which is specifically used to find mutations.
Biomarker tests find changes in your DNA as well as proteins specific to your tumor. A doctor will get a report that shows which biomarkers are in your cancer or blood.
The biomarkers can help point a doctor to the targeted treatment or immunotherapy that’s most likely to work against your cancer.
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. The search is on for more biomarkers, which will hopefully lead to new lung cancer treatments.
The Food and Drug Administration (FDA) has approved treatments for many biomarkers, but these medications don’t work in people without biomarkers.
The FDA has approved more than 20 targeted therapies for people with specific lung cancer biomarkers.
There’s one targeted therapy for KRAS-positive lung cancer:
- sotorasib (Lumakras)
EGFR-positive lung cancers are mostly treated with a group of drugs called EGFR inhibitors. Your options will vary based on factors such as your mutation subtype and whether your cancer has metastasized:
- afatinib (Gilotrif)
- dacomitinib (Vizimpro)
- erlotinib (Tarceva)
- gefitinib (Iressa)
- mobocertinib (Exkivity)
- necitumumab (Portrazza)
- simertinib (Tagrisso)
There’s one other type of targeted therapy for EGFR-positive lung cancer, specifically the EGFR exon 20 insertion mutation:
- amivantamab-vmjw (Rybrevant), an antibody treatment
ALK-positive lung cancers, including those involving the EML4-ALK mutation, are treated with these ALK inhibitors:
- alectinib (Alecensa)
- brigatinib (Alunbrig)
- ceritinib (Zykadia)
- crizotinib (Xalkori)
- lorlatinib (Lorbrena)
METex14-positive lung cancer has two approved targeted therapies:
- capmatinib (Tabrecta)
- tepotinib (Tepmetko)
Treatment for BRAF-V600E-positive lung cancer involves a combination of two drugs:
- dabrafenib (Tafinlar)
- trametinib (Mekinist)
There’s one targeted therapy for HER2-positive lung cancer:
- fam-trastuzumab deruxtecan-nxki (Enhertu)
ROS1-positive lung cancers are treated with these drugs:
- ceritinib (Zykadia)
- crizotinib (Xalkori)
- entrectinib (Rozlytrek)
- lorlatinib (Lorbrena)
Ceritinib (Zykadia) and lorlatinib (Lorbrena) aren’t FDA approved to treat ROS1-positive lung cancers. They’re considered off-label drugs for this NSCLC type.
OFF-LABEL DRUG USE
Off-label drug use means a drug that’s approved by the Food and Drug Administration (FDA) for one purpose is used for a different purpose that hasn’t yet been approved.
However, a doctor can still use the drug for that purpose. This is because the FDA regulates the testing and approval of drugs but not how doctors use drugs to treat their patients.
So your doctor can prescribe a drug however they think is best for your care.
RET-positive lung cancer is treated with drugs called RET inhibitors:
There are two approved targeted therapies for NTRK-positive lung cancer:
- entrectinib (Rozlytrek)
- larotrectinib (Vitrakvi)
Immunotherapy drugs for NSCLC block the proteins PD-1, PD-L1, or CTLA-4.
PD-1 and PD-L1 inhibitors include:
- atezolizumab (Tecentriq)
- cemiplimab-rwlc (Libtayo)
- durvalumab (Imfinzi)
- nivolumab (Opdivo)
- pembrolizumab (Keytruda)
There’s one CTLA-4 inhibitor:
- ipilimumab (Yervoy)
Biomarkers have improved both the diagnosis and treatment of lung cancer. This has led to new and more precise treatments. If you have a lung cancer diagnosis, ask a doctor whether you should have biomarker testing.
If your cancer doesn’t test positive for a biomarker that has an available treatment, find out if you can enroll in a clinical trial.
Investigators are testing many possible lung cancer treatments in clinical trials. You might qualify to try a drug that the FDA or other federal agencies haven’t approved yet.
If you live in the United States, you can get started by visiting the website of the