If you have been diagnosed with non-small cell lung cancer (NSCLC), one of the first discussions with your doctor should be to test your tumor tissue for cancer biomarkers. Biomarkers can include gene changes or high levels of proteins known to cause cancer. You can give your doctor important information about your cancer, including how it might respond to treatment.
“According to National Comprehensive Cancer Network guidelines, anyone with stage 2 or higher lung cancer should undergo molecular testing,” said Dr. David Tom Cooke, chief of general thoracic surgery at UC Davis Health. “There are FDA-approved therapies that target the key genetic mutations involved in lung cancer and have been shown to improve disease-free survival.”
Cooke noted that although guidelines are clear, not all people with lung cancer receive an initial biomarker test immediately after diagnosis. “Don’t be afraid to ask your doctor for a test before starting treatment,” he said. “Just politely say, ‘I would like my tumor to undergo biomarker testing or next-generation sequencing.'”
Only small samples are required for biomarker testing
Lung cancer is diagnosed with a bronchoscopy, a minimally invasive procedure that allows your doctor to look inside your lungs. The doctor uses a thin tube with a light and camera on it. If they see a cell mass in your lung, they use tiny tools to remove a piece of the tumor and send it to the lab.
To perform biomarker testing for lung cancer, doctors in the hospital laboratory perform tests on the tumor sample taken during your bronchoscopy. Ideally, your doctor will order next-generation sequencing, which uses a sample to test for many genetic mutations.
If your doctor was unable to perform a lung biopsy to remove tumor cells, some biomarkers can also be identified with a blood test called a liquid biopsy. Your doctor will explain more about what they need to do your biomarker testing.
Lung cancer biomarkers
Genetic biomarkers often appear as mutations in one or more of these genes:
- EGFR – Epidermal growth factor receptor (EGFR) protein supports cell growth. Changes or mutations in the EGFR gene, most commonly EGFR exon 19 deletions or EGFR L858R mutations, can lead to lung cancer. These mutations tell doctors what type of change has occurred in the DNA. EGFR mutations are responsible for 10-15% of lung cancer cases in the United States. People who develop EGFR-positive lung cancer are most likely to be younger non-smokers. Asian people are also more likely to have EGFR mutations.
- ALK – The gene for anaplastic lymphoma kinase (ALK) is already active in humans in the womb and then normally switches off before birth. In some people, the ALK gene turns on again later in life and fuses with another gene, which can lead to cancer. ALK mutations are responsible for approximately 4% of lung cancers in the United States
- ROS1 – In ROS1-positive lung cancer, the ROS1 gene is fused to another gene, usually CD74, to cause the cancer. Alterations in the ROS1 gene occur in approximately 1–2% of patients with lung cancer and are generally found in adenocarcinomas.
- BRAF V600E – In this mutation of the BRAF gene, one amino acid is exchanged for another. BRAF V600E mutant cancers most commonly occur in melanoma, but can also occur in lung adenocarcinoma.
- NTRK – In a cancer that tests positive for an NTRK gene fusion (pronounced “en-trek”), part of the NTRK gene fuses with part of another gene. This mutation is relatively rare in lung cancer. NTRK fusions are also observed in breast and colon tumors, as well as in more than 20 other tumor types.
- MET – Currently, two possible changes in the MET gene can cause lung cancer. In MET exon 14 skipping, a mutation causes a specific part of the gene to be removed. In MET gene amplification, there are too many copies of the gene.
- RET – The most common mutation of the RET gene in lung cancer is a fusion with another gene. This type of mutation is also called RET rearrangement.
- KRAS – The KRAS gene (pronounced “kay-ras”) helps control communication between cells. A G12C mutation of the KRAS gene is a common cause of lung cancer.
- HER2 – Human epidermal growth factor receptor 2 (HER2) acts as an on/off switch for cells, similar to EGFR. When HER2 is broken, it gets stuck in the “on” position, allowing cancer cells to grow. In lung cancer, the HER2 gene can have either a mutation or too many copies. Your doctor may also refer to HER2 as ERBB2. Mutations in the HER2 gene also play a role in other types of cancer, including breast cancer.
- NRG1 – This mutation occurs when two parts of a gene fuse together, resulting in abnormal cell growth and sometimes cancer. NRG1 gene fusions are commonly found in a subtype of NSCLC called invasive mucinous adenocarcinoma.
Protein biomarkers can provide information about whether the cancer cells respond to immunotherapy. Immunotherapy trains the immune system to recognize and attack cancer cells.
- PD-L1 – PD-L1 is a protein found on the surface of some cells. When cancer cells have high levels of PD-L1, they turn off immune cells responsible for fighting diseases, including cancer. PD-L1 blocks immunotherapy, but drugs known as PD-L1 inhibitors prevent this and allow the immune system to destroy cancer cells.
- TMB – Tumor mutation burden measures the number of mutations within a tumor. The mutations lead to the production of abnormal proteins by the cancer cells. Immunotherapy may work if your tumor has at least one abnormal protein that the immune system can recognize.
Read: Understanding the different types of lung cancer >>
Therapies for lung cancer
There is currently at least one targeted therapy to treat each of these genetic mutations. “Targeted therapies” are so called because they target only the specific cancer-causing protein in each tumor.
One of the most common classes of targeted therapy drugs for lung cancer are the so-called tyrosine kinase inhibitors (TKIs). Your doctor will choose the right TKI for your tumor type, mutation, stage of disease and any previous treatments.
Targeted therapies do not work in people who do not have the specific mutation that each drug is designed to treat. But people with lung cancer who don’t have actionable genetic mutations can receive chemotherapy and/or immunotherapy. Immune checkpoint inhibitors, a form of immunotherapy, can often be used to treat people whose tumors have high levels of PD-L1 or high levels of TMB.
Lung cancer remains a serious diagnosis, but your doctor is more likely than ever to have information about your tumor that they can use to develop the treatment most likely to treat your cancer. And when it comes to lung cancer, knowledge – and personalized medicine thanks to today’s latest biomarkers – can make all the difference.
This educational resource was created with support from Daiichi.
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