Every cell in your body contains genes that control how it functions, grows, and even how it dies. Mutations in these genes can disrupt the process normal cells undergo, ultimately causing them to behave abnormally and become cancerous.  

Different types of mutation exist, stemming from various causes. Somatic mutations occur over your lifetime and are usually caused by environmental exposures, including smoke-related toxins. Germline mutations, on the other hand, are inherited. Several somatic gene mutations are related to non-small cell lung cancer.

Understanding the specific gene mutations in a non-small cell lung cancer patient can direct the oncology team on the most effective treatments.

Gene Mutations Associated with Non-small Cell Lung Cancer

The following genes are known to be related to genetic mutations found in non-small cell lung cancer:

EGFR

The Epidermal growth factor receptor (EGFR) is related to approximately 23% of non-small cell lung cancer (NSCLC) diagnoses. The EGFR gene plays a role in cellular growth and division. Patients diagnosed with lung cancer that is associated with an EGFR mutation are typically identified as having EGFR-positive cancer.

BRAF

The BRAF protein plays an important role in regulating cell division and growth. When mutations occur within the BRAF gene, it can produce an abnormal protein that sends abnormal signals for cell growth, resulting in uncontrolled cell growth and the development of lung cancer. This protein typically works with another protein known as MEK in the cell growth regulation process. Because of this, lung cancer doctors often consider the MEK protein when choosing targeted treatments for BRAF mutations. This genetic mutation is commonly found in individuals with a smoking history and impacts approximately 3% to 4% of patients diagnosed with non-small cell lung cancer (NSCLC).

KRAS

The KRAS gene produces the K-RAS protein, which sends signals that control cell growth, replication, and differentiation. In approximately 30% of non-small cell lung cancer (NSCLC) cases, mutations in the KRAS gene have been identified. These mutations are frequently found among individuals with a smoking history. Additionally, KRAS mutations may occur in combination with other genetic alterations. 

MET

The MET gene mutation, frequently detected in non-small cell lung cancer, can mutate in two primary ways. One is called MET gene amplification, where multiple copies of the gene are present. Because MET is a growth receptor, too many copies of this gene leads to accelerated cancer cell growth.

The other gene mutation related to MET, called exon 14 skipping, occurs when there’s a disruption in the cell breakdown process. Typically, the CBL protein works with exon 14 to break down the MET protein when it’s no longer needed. However, when the MET gene is mutated in this manner, exon 14 can be bypassed, prolonging MET receptor activity and promoting tumor growth.

RET

Alterations in the RET gene can result in rearrangement and fusion with other genes, resulting in a "fusion" protein that is overactive and promotes tumor growth. Two FDA-approved drugs target these fusion proteins, effectively stopping and reversing tumor growth. RET is frequently included in various genomic panels for cancer care. Such RET alterations are found in 1-2% of lung cancer cases.

ALK

ALK stands for anaplastic lymphoma kinase, a gene that plays an important role in the development of the gut and nervous system in the womb. Normally, this gene deactivates before birth. However, in some individuals, it may reactivate and undergo fusion with other genes, leading to conditions such as lung cancer. 

These ALK gene mutations, particularly ALK fusions or rearrangements, are more frequently found among lung cancer patients who are younger and have no smoking history. 

ROS1

Mutations in the ROS1 gene are relatively rare among lung cancer patients, presenting only 1% to 2% of cases. If your lung cancer specialist identifies a mutation in the ROS1 gene, your diagnosis will be ROS1-positive cancer. This particular gene can merge with other genes, which can trigger uncontrolled cell growth, ultimately leading to cancer. ROS1 gene mutations are more frequently seen in patients who are younger and have no history of smoking.

NTRK

NTRK proteins can also experience fusions. This is another alteration that has FDA-approved oral medications. NTRK is very rare, accounting for less than 1% of lung cancer cases. 

TP53

The TP53 gene plays an important role in cellular regulation as it helps a protein called P53 suppress damaged cells, thus reducing the risk of cancer development. TP53 gene mutations are commonly involved in NSCLC and related to about half of all cases. Despite this, routine screening for this gene is not standard practice, mainly due to the lack of targeted treatments that are effectively designed for it. 

How Are Genetic Mutations Identified in Non-Small Cell Lung Cancer Patients?

If you are diagnosed with non-small cell lung cancer, your doctor may suggest genetic mutation testing, often called biomarker testing. These tests can be done using various methods.

Most patients had a biopsy to confirm the presence of lung cancer. Biomarker testing can be run on the tumor cells removed during the biopsy. 

Next-generation sequencing (NGS) is another common method that simultaneously searches for multiple biomarkers. Sometimes, a liquid biopsy may be recommended, using blood samples to identify biomarkers. 

Targeted Therapies for Advanced Non-Small Cell Lung Cancer with Genetic Mutations

The recommended treatment plan for NSCLC is highly personalized, taking into account your unique diagnosis. Biomarkers and genetic mutations play a crucial role in guiding the treatment process. For instance, late-stage or recurrent non-small cell lung cancer with genetic mutations may be treated with targeted therapies that hone in on specific cell proteins. This reduces damage to healthy cells, which reduces side effects.

Targeted approaches for non-small cell lung cancer with genetic mutations include therapies for:

  • BRAF-positive lung cancer can be treated with a combination of targeted therapies or a combination of immunotherapy and chemotherapy. 
  • KRAS mutations may allow NSCLC patients to receive other treatments, including surgery, radiation, chemotherapy, or immunotherapy. The stage of lung cancer determines if a combination of these treatments is necessary.
  • ALK-positive and EGFR-positive lung cancer may be treated with a type of targeted therapy drug called tyrosine kinase inhibitors (TKIs). While these drugs can help control lung cancer for a time, they do not provide a cure. 

Your lung cancer specialists will create a treatment plan tailored to the genetic profile of the cancer, its stage, and your overall health. Ongoing clinical trials, such as those conducted by Compass Oncology, help advance targeted therapy options for lung cancer.

Lung Cancer Targeted Therapies in Portland and Vancouver 

At Compass Oncology, we are committed to supporting you through your lung cancer journey. We offer advanced technology and tailored treatment plans for each patient's needs, including the latest biomarker testing. We also welcome those seeking a second opinion on their lung cancer diagnosis and treatment plan. 

For comprehensive lung cancer care, schedule a consultation with one of our oncologists at a location convenient to you. Our cancer clinics are located in Portland, OR, and Vancouver, WA.

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