Every cell contains genes that dictate its functions, growth, and even when the cell should die. When there is a change in a gene, it disrupts how the cells normally grow and divide. This change is called a genetic mutation. Mutations of some genes can result in abnormal cell behavior related to the development of non-small cell lung cancer.
Genetic mutations fall into one of two categories: germline or somatic. Germline mutations are hereditary and passed down from one or both parents. Most of the genetic mutations related to lung cancer are not germline. In contrast, somatic mutations occur within an individual due to external factors, such as their environment and exposure to harmful substances. Somatic mutations generally related to lung cancer development are primarily due to chemicals present in cigarette smoke.
Patients are tested to see if they show one or more known genetic mutations related to non-small cell lung cancer. Some patients show no genetic mutations, while others have more than one. The process of identifying the somatic genetic mutations is called biomarker testing. The lung cancer cells removed during a biopsy or surgery are tested. The results allow the oncologist to create personalized treatment plans tailored to the patient, including treatments that can specifically target the genetic mutation.
Gene Mutations Associated With Non-small Cell Lung Cancer
Biomarker testing, also called genomic testing, will be completed on the tumor or tumor sample. This can take a few weeks to report back. Currently, the following genes are evaluated during the biomarker tests:
EGFR
EGFR gene mutations account for approximately 23% of non-small cell lung cancer cases. EGFR refers to the epidermal growth factor receptor, which plays an important role in cellular growth and division. When lung cancer is associated with mutations in the EGFR gene, it is typically classified as EGFR-positive cancer.
ALK
The anaplastic lymphoma kinase (ALK) gene plays an important role in developing a fetus’s gut and nervous system. Ordinarily, this gene deactivates before birth but can become reactivated or fuse with other genes, eventually leading to lung cancer.
Although commonly associated with lymphoma, ALK mutations can also be found in non-small cell lung cancer patients, accounting for up to 7% of cases. These genetic mutations are more common among younger individuals diagnosed with lung cancer and those who have never smoked.
BRAF
The BRAF protein is responsible for regulating cell division and growth. Mutations within the BRAF gene can produce an abnormal protein that sends incorrect signals for cell growth, which could result in uncontrolled cell growth and the development of cancer. The BRAF protein typically works with MEK, another protein involved in cell growth regulation. Because of this, lung cancer specialists may reference MEK when discussing the best treatment to target a BRAF mutation. This gene mutation is often seen in individuals with a history of smoking and impacts approximately 3% to 4% of non-small cell lung cancer patients.
KRAS
The KRAS gene produces the K-RAS protein, an important component in the signaling pathways that control cell growth and differentiation. In approximately 30% of non-small cell lung cancer (non-small cell lung cancer) cases, mutations in the KRAS gene have been identified, especially among individuals with a smoking history. Additionally, KRAS mutations may occur in combination with other genetic mutations, including TP53, STK11, and KEAP1.
MET
In lung cancer, the MET gene can mutate in two distinct ways. One is known as MET gene amplification, signifying the presence of additional gene copies. Given that MET functions as a growth receptor, an elevated number of these genes can lead to excessive growth signaling, ultimately increasing the growth of cancer cells.
The second mutation related to MET is called exon 14 skipping. This mutation disrupts an essential phase in the cellular breakdown process. Typically, a protein named CBL helps break MET down when it is no longer needed.
CBL joins with MET, and exon 14 plays a role in this breakdown process. Mutations in the MET gene lead to the skipping of exon 14, resulting in the prolonged presence of MET proteins, which may encourage cell growth.
ROS1
ROS1 gene mutations are relatively rare in lung cancer, present in only about 1% to 2% of cases. If testing shows your cancer is related to a mutation in the ROS1 gene, your lung cancer doctor will refer to it as ROS1-positive cancer. This mutation involves the fusion of the ROS1 gene with another gene, which can trigger uncontrolled cell growth, leading to cancer. ROS1 gene mutations are more frequent in younger lung cancer patients who have never smoked.
RET
Alterations in the RET gene can lead to it moving around and fusing with other genes, resulting in a “fusion” protein that exhibits hyperactivity and promotes tumor growth. Two FDA-approved drugs specifically target these fusion proteins, effectively inhibiting and reversing tumor growth. Geometric panels frequently include RET in their cancer testing. In lung cancer, RET mutations are present in approximately 1-2% of cases.
NTRK
Fusions in NTRK proteins represent a rare alteration, with FDA-approved oral medications available for treatment. This mutation occurs in less than 1% of lung cancer cases.
TP53
The TP53 gene plays an important role in regulating cells, acting as a tumor suppressor. It produces the P53 protein, targeting abnormal cells, thereby lowering cancer risk. Mutations in TP53 are commonly involved in non-small cell lung cancer, accounting for roughly half of all cases. Despite its prevalence, routine testing for this mutation is uncommon because no specialized therapy is available.
Testing Process for Genetic Mutations
If the tissue removed during the biopsy or surgery is unavailable for testing, next-generation sequencing (NGS) is another common method. This machine is used to screen for multiple biomarkers at the same time. Another alternative approach your doctor may suggest is a liquid biopsy, which uses a blood sample to test for biomarkers.
For lung cancer, there are two primary methods to test for genetic changes: one involves using pathology tissue from a tissue sample, and the other requires drawing blood to search for circulating cancer cells and DNA in the bloodstream. Your lung cancer doctor may opt for one or both tests, possibly during the same visit, to enhance detection effectiveness.
Advances in Lung Cancer Treatment by Targeting Genetic Mutations
Lung cancer biomarker testing is a pivotal step in personalized cancer care, enabling your oncology team to pinpoint and administer drugs that directly target the specific genetic mutations within the tumor. If no mutations are detected, your care team will suggest alternative lung cancer treatment methods that might be effective for you.
Patients diagnosed with stage IV (4) or recurrent non-small cell lung cancer can benefit from targeted therapies. They “target” specific proteins or genetic mutations that cause cell overgrowth while causing minimal damage to the healthy surrounding cells. Ongoing research explores how these treatments can be incorporated into the treatment plans for earlier stages of non-small cell lung cancer.
Common treatment approaches for non-small cell lung cancer based on genetic mutations include:
ALK-positive and EGFR-positive lung cancers are often treated with targeted therapy pills known as tyrosine kinase inhibitors (TKIs). These medications can manage the disease for extended periods but are not a cure.
BRAF-positive lung cancer is commonly treated with a regimen of targeted therapies or a mix of immunotherapy and chemotherapy.
KRAS mutations are frequently treated with various first-line treatments such as surgery, radiation, chemotherapy, or immunotherapy. Depending on the lung cancer stage, a combination of these treatment types may be used.
Targeted therapy may be combined with other lung cancer treatments, such as chemotherapy, depending on your specific situation. The right set of treatments for each patient is determined by the lung cancer specialist, who consults with other physicians on the care team and considers several factors, including the patient’s overall health and ability to go through treatment.
Ongoing clinical trials are at the forefront of developing new targeted therapies for lung cancer based on distinct genetic mutations. The lung cancer experts at Affiliated Oncologists are actively involved in these trials, enabling us to offer the latest treatments to our patients.
Biomarker Testing for Non-Small Cell Lung Cancer is Available through Affiliated Oncologists
Affiliated Oncologists, located throughout the south Chicago suburbs, offers state-of-the-art approaches for diagnosing and treating lung cancer. Our cancer experts can help pinpoint your lung cancer type and recommend a personalized treatment plan, including targeted therapies for specific genetic mutations when available.
If you were recently diagnosed with lung cancer, request an appointment with one of our lung cancer specialists at our locations in Chicago Ridge, Mokena, Hazel Crest, Oak Lawn, Orland Park, and Palos Heights, IL.