Gene mutations associated with non-small cell lung cancer include EGFR, HER2, and more. Lung cancer mutations can determine your options for testing and treatment.
Genes are the instructions that inform how your body functions. They tell your cells which proteins to make. Proteins control how quickly cells grow, divide, and survive.
Sometimes genes change. This may happen before a person is born or later in life. Gene changes are called mutations, and they can affect certain functions in the body.
Gene mutations can prevent your DNA from repairing itself and can also cause cells to grow uncontrollably or live for too long. Eventually, these extra cells can form tumors, which is how cancer starts.
Certain gene mutations are linked to non-small cell lung cancer (NSCLC). Having one of these mutations could affect the type of treatment a doctor recommends.
The gene mutations that cause lung cancer can happen in one of two ways.
Germline mutations are hereditary mutations. They’re passed genetically from a parent to their baby through an egg or sperm.
Somatic mutations are acquired mutations. They’re the most common cause of cancer.
Somatic mutations occur when you’re exposed to damaging substances over the course of your lifetime. These substances may include:
- chemicals
- tobacco
- ultraviolet (UV) radiation
- viruses
A few different gene mutations help NSCLCs spread and grow.
Tumor protein p53 (TP53)
The TP53 gene is responsible for the production of the tumor protein p53. This protein monitors cells for DNA damage and acts as a tumor suppressor. This means it keeps damaged cells from growing out of control or growing too fast.
TP53 mutations are common in cancers and are found in 40% to 51% of all cases of NSCLC. They’re usually acquired and happen in both smokers and people who have never smoked.
Research suggests that TP53 mutations combined with EGFR, ALK, or ROS1 mutations are linked to a shorter survival time for people with NSCLC.
Because there’s not yet an established targeted therapy for TP53 mutations, there’s debate about whether doctors should always test for them in people with cancer. Research into targeted TP53 therapies is ongoing.
KRAS
The KRAS mutation is found in about 30% of all NSCLCs. It’s more common in people who smoke.
The outlook for people with this type of mutation is less favorable than it is for people who don’t have it.
The STK11 mutation often appears with the KRAS mutation. Experts are unsure if the STK111 mutation is significant or what effect it has on treatment options.
Epidermal growth factor receptor (EGFR)
Epidermal growth factor receptor (EGFR) is a protein on the surface of cells that helps them grow and divide. Some NSCLC cells have too much of this protein, which makes them grow faster than usual.
According to the American Lung Association, EGFR-positive cancers account for around 10% to 15% of all lung cancers in the United States.
These mutations are
EGFR mutations include the:
- EGFR exon 19 deletion mutation
- EGFR exon 20 insertion mutation
- EGFR exon 21 L858R point mutation
- EGFR exon T790M mutation
The EGFR exon 19 deletion mutation and EGFR exon 21 L858R point mutation are the most common. They respond to targeted therapies known as EGFR inhibitors.
Less common EGFR mutations don’t typically respond to these targeted therapies.
Anaplastic lymphoma kinase (ALK)
Research from 2017 found that
The ALK mutation is common in younger people and nonsmokers.
The EML4-ALK mutation occurs when the ALK gene fuses with the echinoderm microtubule-associated protein-like 4 (EML4) gene. It’s also more common in people who have never smoked.
Mesenchymal–epithelial transition (MET) and METex14
The MET gene is changed in
MET exon 14 deletion (METex14) is a type of MET mutation that’s been linked to around 3% of NSCLCs.
A 2024 study found that the PIK3CA gene mutation was present in 46 of 810 (up to 6%) of lung cancer samples. It’s more common in squamous cell lung carcinomas than in adenocarcinomas.
Did you know?The three main types of non-small cell lung cancer (NSCLC) are:
- adenocarcinoma, which is the most common form of lung cancer overall
- large cell carcinoma
- squamous cell carcinoma
BRAF and BRAF V600E
Up to 3.5% to 4% of NSCLCs test positive for BRAF mutations.
Most people who have these mutations are current or former smokers. These mutations are also more common in females than in males.
One subtype is known as the BRAF V600E mutation. It accounts for half of all BRAF mutations.
Human epidermal growth factor receptor 2 (HER2)
Between 1% and 4% of NSCLCs involve the human epidermal growth factor receptor 2 gene mutation, more commonly known as HER2.
It’s most common in people with adenocarcinomas and people who have never smoked.
Other mutations
Some of the less common mutations linked to NSCLC include:
- NRAS
- neurotrophic tyrosine receptor kinase (NTRK)
- RET
- ROS1
According to research from this 2024 study and this 2021 research review, each of these mutations affects less than 2% of NSCLC cases.
When you’re first diagnosed with NSCLC, your doctor may test you for certain gene mutations.
These tests are called molecular analysis, biomarker tests, or genomic tests. They give your doctor a genomic profile of your tumor.
Knowing whether you have one of these mutations may help your care team decide which treatments might work best for you. Targeted therapies work on some lung cancer mutations but not all.
Genetic tests use a sample of tissue from the tumor, which your doctor removes during a biopsy. The tissue sample is sent out to a lab for testing. A blood test can also be used to detect the EGFR gene mutation.
According to the American Lung Association, it may take 1 to 2 weeks to get the results of your genetic tests.
The treatment your doctor recommends will be based on the results of your genetic test as well as your type and stage of cancer.
A few targeted drugs treat NSCLC gene mutations. You may take these as a solo treatment. They can also be paired with another targeted therapy, chemotherapy, or other lung cancer treatments.
At the moment, there are no targeted therapies for cancers involving TP53, NRAS, or PIK3CA gene mutations. If no drug is currently available for your specific mutation, you may qualify for a clinical trial. These studies test new targeted therapies.
Getting into a trial could give you access to a new drug for your NSCLC type before it’s available to everyone else.
KRAS
In 2021, the Food and Drug Administration (FDA) approved sotorasib (Lumakras), the first KRAS inhibitor for lung cancer.
EGFR
The EGFR protein helps cancers with the EGFR mutation grow. EGFR inhibitors block signals from the EGFR protein.
These EGFR inhibitors can treat the EGFR exon 19 deletion and EGFR exon 21 L858R point mutations:
- dacomitinib (Vizimpro)
- erlotinib (Tarceva)
- gefitinib (Iressa)
These drugs are specifically used to treat the EGFR exon 20 insertion mutation:
Osimertinib (Tagrisso) is the only drug currently available to treat the EGFR exon 19 deletion, EGFR exon 21 L858R point, and EGFR exon T790M mutations.
Other drugs used to treat various EGFR mutations include:
- afatinib (Gilotrif), an EGFR inhibitor
- necitumumab (Portrazza), an EGFR inhibitor that must be taken with the chemotherapy drugs gemcitabine (Infugem) and cisplatin
These may be used for certain cases of metastatic EGFR-positive lung cancer.
ALK
Drugs that target ALK gene mutations include:
People who have cancer with the EML4-ALK mutation would also take these targeted drugs.
MET and METex14
Treatments for the METex14 mutation include the drugs:
- capmatinib (Tabrecta)
- tepotinib (Tepmetko)
There are currently no FDA-approved targeted therapies for other MET mutations. But if you participate in a clinical trial, you may be able to receive a MET inhibitor that targets these mutations.
BRAF and BRAF V600E
The drugs that target BRAF V600E mutations are:
These medications must be taken in combination.
Other BRAF mutations are currently treated with immunotherapy or chemotherapy as opposed to targeted therapies.
HER2
In August 2022, the FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu), the first targeted therapy for people with the HER2 mutation.
Enhertu was previously approved to treat other cancers, such as breast and stomach cancers.
Other mutations
Two drugs are available to treat cancers caused by the NTRK mutation:
- entrectinib (Rozlytrek)
- larotrectinib (Vitrakvi)
The following drugs are RET inhibitors:
These targeted therapies treat ROS1-positive lung cancers:
The FDA has only approved ceritinib (Zykadia) and lorlatinib (Lorbrena) to treat NSCLCs with ALK mutations. Using these medications to treat ROS1-positive lung cancers is considered off-label drug use.
OFF-LABEL DRUG USE
Off-label drug use means a drug that’s approved by the 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.
NSCLC treatment used to be one-size-fits-all. Everyone received the same regimen, which often involved chemotherapy.
Today, a number of treatments target specific gene mutations. Your doctor should test your tumor when you’re diagnosed and let you know if you’re a good candidate for a targeted drug.
In some cases, you may also qualify for a clinical trial.