Most lung cancers are NSCLCs. Many people receive a diagnosis of NSCLC after it has spread to other parts of their body.

Changes in the DNA of tumor cells can make the cancer spread faster. By better understanding the DNA in these mutations, doctors can identify the most effective treatment for a person.

According to the Lung Cancer Foundation of America, everyone with a lung cancer diagnosis should undergo this type of biomarker testing.

Genetic mutations are a natural part of life, and many are harmless. However, when the cells in a person’s lungs mutate in certain ways, NSCLC can develop.

These NSCLC-causing mutations can arise randomly. However, scientists estimate that roughly 90% of lung cancers are linked to tobacco use.

Other causes of genetic mutations that may increase the risk of NSCLC include:

  • alcohol use
  • exposure to ionizing radiation
  • exposure to radon
  • exposure to asbestos

There are many different kinds of genetic mutations.

When an expert tests a sample of lung tissue, they look for genetic mutations known to cause NSCLC.

A 2020 study notes that mutations in the following genes can be associated with NSCLC:

  • EGFR
  • BRAF
  • ALK
  • RET
  • NTRK
  • ROS1
  • HER2
  • KRAS
  • MET

EGFR exon 20 gene

Around 10% to 30% of NSCLC tumors result from mutations in the epidermal growth factor receptor (EGFR) gene.

Between 85% and 90% of EGFR mutations involve exons 19 and 21. An exon is a specific part of a gene. Ten percent to 15% involve mutations such as the exon 20 insertion. However, the exon 20 mutation is becoming more prevalent as researchers better understand rare gene mutations in NSCLC.

People with exon 20 insertion mutations do not respond well to erlotinib, gefitinib, and the second-generation EGFR inhibitor afatinib.

However, researchers have developed candidate inhibitors that can target the EGFR exon 20 insertion mutant kinase. In the future, these medications may become a treatment option for people with this subtype of NSCLC.

Genetic testing enables doctors to personalize treatment plans based on mutations identified in a person’s cells.

For example, researchers in the 2020 study mentioned above analyzed the genes of 256 people in China with NSCLC. They found that the most common genetic mutations among these participants were to the EGFR, ERBB2, and KRAS genes. Of the total participants, 63% had two or more mutations.

One participant had an uncommon mutation in two genes. This means one of the genes could develop resistance to certain medications, prompting doctors to use a different type of treatment that might be more effective.

When doctors know which genetic mutations are associated with a person’s NSCLC, they can provide the best, most personalized treatment possible.

They can do this using an agent such as a tyrosine kinase inhibitor (TKI), a drug that can cross the cell membrane. By blocking various genes and proteins from carrying out their functions, these drugs interfere with the processes that drive cancer cell growth and division.

Different genetic mutations require different TKIs, and some TKIs can target multiple genetic mutations.

The National Cancer Institute (NCI) lists the following common TKIs and the gene mutations they target:

  • EGFR inhibitors: erlotinib, gefitinib, afatinib, osimertinib, dacomitinib
  • BRAF inhibitors: dabrafenib
  • ALK inhibitors: crizotinib, entrectinib, ceritinib, alectinib, brigatinib, and lorlatinib
  • RET inhibitors: selpercatinib
  • NTRK inhibitors: larotrectinib
  • ROS1 inhibitors: crizotinib and entrectinib

Some mutations have proven more resistant to existing TKIs. However, scientists are working hard to develop more effective treatment options.

For example, a 2019 study from Korea reports that earlier research found HER2 TKIs to be relatively ineffective. But the researchers note that some newer drugs may better target the HER2 gene. These include:

  • ado-trastuzumab emtansine (T-DM1)
  • afatinib
  • dacomitinib

Similarly, the NCI notes that the KRAS inhibitor sotorasib may reduce tumor size in people with NSCLC who have a mutation in that gene.

According to the NCI, doctors perform genetic testing by first taking a small sample of abnormal-looking tissue from a person’s lungs. This is known as a biopsy. Doctors do this by using a very fine needle that sucks up a sample of lung tissue.

They can locate the tissue using imaging technology, such as a CT scan, or by performing a procedure called bronchoscopy, which involves inserting a flexible fiberoptic scope into the person’s airway. Sometimes, the scope has an ultrasound probe at the tip to help locate cancerous tissue.

The doctors then send the sample to a laboratory for testing to determine the type of cancer and its stage.

Certain gene mutations can cause NSCLC. Doctors can choose the most effective treatment depending on which genes are faulty.

Since not everyone with NSCLC has the same gene mutations, treatment will vary from person to person.

Receiving personalized treatment based on genetic testing can significantly improve a person’s outlook with NSCLC.