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If you have been diagnosed with non-small cell lung cancer (NSCLC), one of the first discussions you should have with your doctor is testing for tumor biomarkers in your tumor tissue. Biomarkers could be genetic changes or high levels of proteins known to cause cancer. They can provide your doctor with important information about your cancer, including the effectiveness of treatment.
“According to National Comprehensive Cancer Network guidelines, anyone with stage 2 or higher lung cancer should undergo molecular testing,” said David Tom Cooke, MD, chief of general thoracic surgery at UC Davis Health. “There are FDA-approved treatments [Administración de medicamentos y alimentos] which address the key genetic mutations in lung cancer and have been shown to improve cancer-free survival.
Cooke mentioned that not all people with lung cancer undergo initial biomarker testing immediately after diagnosis, even though the guidelines clearly state this. “Don’t be afraid to ask your doctor for tests before starting any treatment,” he said. “Just politely say, ‘I would like to have my tumor tested for biomarkers or next-generation sequencing.'”
Only a small sample is 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 may use a probe that has a light and a camera. When he sees a cell mass in your lung, he uses tiny tools to remove a piece of the tumor and sends it to a laboratory.
To test for lung cancer biomarkers, doctors in the hospital laboratory analyze the tumor sample taken during your bronchoscopy. Ideally, your doctor will order next-generation sequencing, which uses a sample to analyze and detect many genetic mutations.
If your doctor was unable to perform a lung biopsy to remove tumor cells, some biomarkers can also be identified through a blood test called a liquid biopsy. Your doctor will explain more about what you need to do for your biomarker tests.
Lung cancer biomarkers
Genetic biomarkers often manifest as mutations in one or more of these genes:
- EGFR: Epidermal growth factor receptor (EGFR) protein promotes cell proliferation. Changes or mutations in the EGFR gene, most commonly deletions in the EGFR exon or EGFR L858R mutations, can cause lung cancer. These mutations tell doctors what type of change the DNA has. EGFR mutations occur in 10 to 15% of lung cancer cases in the United States. The people who develop lung cancer with EGFR changes are more likely to be young people who have never smoked. Asians are more likely to have EGFR mutations.
- ALK: The gene for anaplastic lymphoma kinase (ALK) is active in humans in the womb and is normally switched off before birth. In some people, the ALK gene is later activated and fuses with another gene, which can cause cancer. ALK mutations are present in approximately 4% of lung cancers in the United States.
- ROS1: In lung cancers with ROS1 gene mutations, the ROS1 gene fuses with another gene, most commonly CD74, and causes cancer. Alterations in the ROS1 gene occur in approximately 1 to 2% of lung cancer patients and are usually found in adenocarcinomas.
- BRAF V600E: In this mutation of the BRAF gene, one amino acid is replaced by another. Cancers with BRAF V600E mutations most commonly occur in melanoma, but can also be found in lung adenocarcinoma.
- NTRK: In a cancer where an NTRK gene fusion is detected, a section of the NTRK gene is fused to a section of another gene. This mutation is relatively rare in lung cancer. NTRK fusions can also be seen 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 exon 14 skipping of the MET gene, a mutation causes a specific part of this gene to be deleted. In MET gene amplification, there are many copies of this 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 a RET gene rearrangement.
- KRAS: The KRAS gene promotes communication between cells. A G12C mutation of the KRAS gene is a common cause of lung cancer.
- HER2: Human epidermal growth receptor 2 (HER2) acts as an on-off switch for cells, very similar to EGFR. When HER2 is altered, it gets stuck in the “on” position, allowing cancer cells to multiply. In lung cancer, the HER2 gene could have a mutation or too many copies. Your doctor may also refer to HER2 as ERBB2. HER2 gene mutations may also play an important role in other types of cancer, including breast cancer.
- NRG1: This mutation occurs when two parts of a gene fuse, resulting in abnormal cell proliferation and sometimes cancer. NRG1 gene fusions are commonly found in a subtype of NSCLC called invasive mucinous adenocarcinoma.
Protein biomarkers can provide information about how cancer cells respond to immunotherapy. Immunotherapy teaches 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, immune cells that fight disease, including cancer, are deactivated. PD-L1 blocks immunotherapy, but drugs known as PD-L1 inhibitors prevent this and allow the immune system to destroy cancer cells.
- CMT: The tumor mutation burden indicates the number of mutations in a tumor. Mutations cause cancer cells to produce abnormal proteins. 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. They are called “targeted therapies” because they exclusively target specific cancer-causing proteins in each tumor.
One of the most common types of targeted therapy drugs for lung cancer are so-called tyrosine kinase inhibitors (TKIs). Your doctor will select the appropriate TKI for your tumor type, mutation, stage of disease and previous treatments.
Targeted therapies do not work in people who do not have the specific mutation for which the drug was designed. But people with lung cancer that doesn’t have genetic mutations that could be exploited could receive chemotherapy or immunotherapy. Immune checkpoint inhibitors, a form of immunotherapy, can often be used to treat people with tumors that have high levels of PD-L1 or CMT.
Lung cancer remains a serious diagnosis, but your doctor may have information about your tumor that can be used to develop the most effective treatment for your specific cancer. And when it comes to lung cancer, knowledge (and personalized medicine thanks to the latest biomarkers in science today) can make a difference.
This educational resource was created with support from Daiichi.
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