Certain genetic mutations are more common in lung cancers seen in nonsmokers than in people who smoke. Biomarker testing can point to targeted treatments for specific mutations.

Many possible genetic changes may occur with lung cancer. Biomarker testing gives experts a way to find out more about specific genetic mutations in cancer cells.

Depending on the genetic mutations present, a healthcare professional may recommend different targeted treatments. This means they can choose from among many different approaches for treating NSCLC. No single treatment will work for every individual situation.

Experts divide lung cancer into two main categories: small-cell lung cancer and non-small cell lung cancer (NSCLC). Small-cell cancer occurs more often in people who smoke, and it tends to grow quickly.

When a person receives a diagnosis, it has often already spread to other body parts. Healthcare professionals often recommend chemotherapy and radiation to shrink small-cell lung cancer tumors.

NSCLC includes:

  • adenocarcinoma
  • squamous cell carcinoma
  • large cell carcinoma

It accounts for around 80–85% of lung cancers. Nonsmokers diagnosed with lung cancer most likely have adenocarcinoma.

Though healthcare professionals today rely on biomarker testing more often, they may not always perform the test. A person with NSCLC should ask their doctor to do genetic testing if they have not already.

Many people focus on smoking as a major risk factor for lung cancer. However, individuals who do not smoke can also get lung cancer.

Lung cancer rates in nonsmokers keep rising, according to a 2017 retrospective study, despite overall rates of lung cancer going down.

Experts consider a person a nonsmoker if they have smoked fewer than 100 cigarettes in their life. Data from a 2020 research review show that more than 50% of cases of lung cancer in women worldwide occur in nonsmokers. For men, 15–20% of those with lung cancer do not smoke.

The most common NSCLC genetic mutations in nonsmokers include:

  • EGFR
  • KRAS
  • ALK

EGFR mutations are more common in nonsmokers than in smokers.

However, experts still consider smoking a significant risk factor in the development of NSCLC. According to a 2009 review of studies, other risk factors include:

  • exposure to secondhand smoke
  • air pollution
  • workplace toxins

Nearly all cells in the human body contain genes. Genes tell a cell what to do. When the genetic material in a cell gets damaged, it no longer acts in an expected way. It can start to grow atypically, which can lead to cancer.

When a person gets an NSCLC diagnosis, the first step should always be biomarker testing. Biomarker testing looks at the genetic material in the cells of the tumor tissue and gives the doctor information on which treatments may work best.

Depending on the gene mutation, a person may have targeted treatment options.

These treatments focus on the specific gene mutation found during biomarker testing. This can help slow or stop the growth of the cancerous cells.

Experts recommend that everyone diagnosed with NSCLC receive biomarker testing.

This process will look for mutations in some or all of the following genes:

  • EGFR
  • ALK
  • ROS1
  • BRAF
  • KRAS
  • MET
  • NTRK
  • RET
  • PDL-1

Some of these mutations occur more commonly than others. A 2017 study found that EGFR mutations occurred in 36% of people who never smoked, compared with 8% of smokers.

The same study also found a much higher mutation incidence in the ALK gene. It occurred in 26% of never-smokers — a significantly higher percentage than the 4% of smokers who had a mutation in the ALK gene.

ROS1 gene fusions may occur less often but have a higher chance of occurring in people who do not smoke. This gene mutation occurs in about 1–2% of NSCLC cases, according to the 2017 study data.

Even if a person has one of the less common genetic mutations, they will still benefit from knowing that information. Promising treatments may be in the works. A person may also find a clinical trial to take part in.

Though rare, some cases of lung cancer involve germline mutations — genetic changes that can be passed down in families. Most mutations in cancer cells are not inherited and will not pass from parent to child.

Some very rare changes in the EGFR genes can make a person more likely to develop lung cancer, per 2018 research. This does not mean the person will develop cancer, but it can increase the risk. In those cases, the individual may want to get frequent screening to catch any lung changes early.

The treatment plan depends on which genetic mutations a healthcare professional sees during biomarker testing. Often, they use a combination of treatments. Factors that influence the best treatment plan include:

  • biomarkers
  • the size and location of the tumor
  • the health of the person

Inhibitor drugs are medications that target specific genetic mutations. They focus on the specific genes that cause the cell to grow atypically. These drugs can slow or stop cancer cells by shutting off the genes causing abnormal growth.

A healthcare professional will choose the specific medication based on what the biomarker testing reveals. A person can take many of these medications orally. Sometimes, they may receive them via infusion.

Occasionally, the inhibitor treatment does not work, or it works for a while, but the cancer comes back. In those cases, experts recommend doing the biomarker testing again. A new mutation may require a different treatment approach.

A person may still receive chemotherapy for NSCLC. This depends on the size of the tumor and the stage of lung cancer.

Biomarker testing can help a doctor decide if chemotherapy may be helpful, according to a 2017 article.

A healthcare professional may also recommend surgery to remove part or all of a tumor as part of the treatment plan. This usually happens only in the early stages of lung cancer. Doctors are more likely to diagnose NSCLC in the later stages.

Although overall rates of lung cancer have declined, rates among nonsmokers continue to rise. Nonsmokers who develop lung cancer most often get adenocarcinoma, a type of NSCLC.

Experts always recommend biomarker testing after a diagnosis of NSCLC. This can find one or several genetic mutations. For many of these mutations, a healthcare professional may recommend targeted treatment therapies.

Several possible biomarkers in NSCLC occur more often in nonsmokers than smokers. These mutations happen in the EGFR, ALK, and ROS1 genes.