Genetic Testing for Lung Cancer

Why It's Done and How It Can Influence Treatment

Genetic testing for lung cancer involves lab tests performed on a blood or tumor tissue sample to determine if the DNA of the cancer cells it contains have gene mutations or other changes that initiate the development or growth of cancer. These tests are performed by a pathologist. If treatable mutations are identified by lung cancer genetic testing, your oncologist can use that information to prescribe medications that "target" the genetic abnormalities specifically.

Types of Mutations

There are two primary types of gene mutations: hereditary and acquired mutations.

Hereditary Lung Cancer Mutations

Also called germline mutations, hereditary lung cancer mutations are those that you are born with. That is, your genetic makeup, from the start, contains an abnormality that increases your risk of developing lung cancer. These mutations can be passed down from parent to child.

Having a hereditary mutation doesn't mean that you will absolutely get lung cancer, but you may be more sensitive to factors that cause cancer. For instance, smoking is a known risk factor for lung cancer. Not everyone who smokes develops the disease, but smoking combined with a specific gene mutation inherited from your parents (such as a known DNA change on chromosome 6) will increase the likelihood that you will develop lung cancer if you smoke.

Acquired Lung Cancer Mutations

It's rare that the genetic changes that cause lung cancer are actually inherited. In most cases, genetic changes are acquired, which means they occur because of exposure to carcinogens that damage cell DNA. These acquired mutations, or somatic mutations, are not present at birth (and do not run in families).

Among the factors that can increase your risk of developing acquired lung cancer mutations are:

  • Tobacco smoke (first hand and second hand)
  • Air pollution
  • Radon
  • Asbestos
  • Certain metals or chemicals
  • Hormone replacement therapy
  • Lung disease

 Tuberculosis, asthma, and COPD are among the diseases that raise the risk of lung cancer. If you have COPD, for instance, your risk of lung cancer is two to four times higher than those without COPD.

While these lifestyle and environmental factors seem to have a more profound influence on the probability of developing lung cancer than family genetics, more research is needed in order to have a clearer understanding of inherited versus acquired mutations.

Importance of Genetic Testing

One of the most exciting advances in the treatment of lung cancer has come from an understanding of genetic changes in lung cancer cells. Whereas in the past we broke lung cancers down into five general types, we now know that no two lung cancers are the same. If there were 30 people in a room with lung cancer, they would have 30 different and unique types of the disease.

If you’ve been recently diagnosed with lung cancer, especially lung adenocarcinoma, your oncologist may have talked to you about genetic testing (otherwise known as molecular profiling or biomarker testing) of your tumor. 

Driver mutations that result in the development of cancer are estimated to be present in as many as 70% of people with lung adenocarcinoma.

It's now recommended that all lung cancer patients have biomarker testing to look for driver mutations that doctors may be able to target with treatments. Detectable mutations include:

What Are Gene Mutations?

Gene mutations are changes to a particular gene in a chromosome. All genes are made up of variable sequences of four amino acids (called bases)—adenine, tyrosine, cytosine, and guanine.

When a gene is exposed to toxins in the environment, or when an accident occurs in cell division, a mutation, or change, may occur. In some cases, it may mean that one base is substituted for another, like adenine instead of guanine. In other cases, bases may be inserted, deleted, or rearranged in some way.

Types of Mutations

There are two types of acquired mutations found in lung cancers: driver mutations and passenger mutations.

Driver Mutations

Driver genes have a direct role in the process by which cancer begins, known as oncogenesis. After initiating the cancer, these damaged, or mutated, genes literally drive the growth of cancerous cells. In lung cancer, there may be more than one type of driver gene. Researchers have estimated that 51% of lung cancers are positive for known driver mutations.

Passenger Mutations

Just as someone may be a passenger in a car, some mutated genes are present in a tumor but are not driving the growth of cancer cells—they are just along for the ride. These neutral cells significantly outnumber the driver cells. Again, the number of passenger genes varies from tumor to tumor, but some tumors may have more than 1,000 of these mutations.

Targeted Therapies

Chemotherapy had traditionally been the treatment of choice for inoperable lung cancer or as adjuvant therapy to support lung surgery. However, the introduction of targeted therapy has changed all that. These drugs make treatment for non-small cell lung cancer more effective.

Targeted therapies are a form of precision medicine, which means they are selected for you based on precise information about your specific disease. This information is garnered from genetic testing of your cancer.

This is much different than conventional chemotherapy where everyone receives the same drugs, or where drugs may only be personalized based on sensitivity to certain side effects. The chemo drugs then attack all rapidly dividing cells—be they cancerous or not. Targeted therapies attack only a particular abnormality present in your cancer cells.

Unlike chemotherapy drugs that carry the risk of toxicity and severe side effects, targeted therapy drugs offer significantly less discomfort and a better quality of life.

With chemotherapy drugs, between 20% and 30% of patients respond to treatment and the progression-free survival rate is estimated to be about three to five months. Now, using targeted therapy drugs to treat you according to the genetic makeup of your cancer allows for higher response rates and longer progression-free survival rates.

Using drugs that target EGFR mutations, for instance, doctors see a 75% response rate and progression-free survival rates of nine to 13 months. With drugs that target ALK rearrangements, the response rate is 60% with a nine-month progression-free survival rate.

Targeted Therapies for Specific Mutations

Researchers are continually studying new ways to treat lung cancer with drugs that work on specific mutations or genetic alterations. These medications can be divided into several categories.

EGFR Inhibitors

Some types of non-small cell lung cancer overproduce EGFR (epidermal growth factor receptor), a protein involved in cell growth and division. The mutated cells grow too fast. These EGFR inhibitor drugs work to slow the growth to keep cancer in check:

  • Tarceva (erlotinib)
  • Iressa (gefitinib)
  • Tagrisso (osimertinib)
  • Vizimpro (dacomitinib)
  • Gilotrif (afatinib)
  • Portrazza (Necitumumab)

ALK Inhibitors

About 5% of non-small cell lung cancers produce an abnormal ALK protein that causes cancer cells to grow and spread. This mutation can be targeted with the following drugs:

  • Xalkori (crizotinib)
  • Zykadia (ceritinib)
  • Alecensa (alectinib)
  • Alunbrig (brigatinib)
  • Lorbrena (lorlatinib)

Drugs to Target ROS1 Rearrangement

About 1% to 2% of non-small cell lung cancers have a rearrangement in a gene called ROS1. This mutation is similar to the ALK rearrangement, so some drugs work on both can work conditions. Drugs that target the abnormal ROS1 protein include:

  • Xalkori (crizotinib)
  • Zykadia (ceritinib)
  • Lorbrena (lorlatinib)
  • Rozlytrek (entrectinib)

Angiogenesis Inhibitors

Angiogenesis is the process by which new blood vessels form. Some targeted therapies can block blood vessels from forming and feeding cancer tumors.

Targeted angiogenesis inhibitors that are approved to treat people with lung cancer may be used with chemotherapy. They include:

  • Avastin (bevacizumab)
  • Cyramza (ramucirumab)

Some rare mutations may also be treated with a BRAF inhibitor, MEK inhibitor, RET inhibitor, or MET inhibitor.

Resistance to Treatment

A challenging problem with targeted treatments is that nearly everyone inevitably becomes resistant to currently available treatments. There are many mechanisms by which this occurs making it difficult to find one solution. Research is ongoing in clinical trials—evaluating both the use of substituting a second drug to target the mutations and combining drugs that use different targets or mechanisms to attack the cancer cell.


Genetic testing is now a routine part of care for lung cancer. If you're diagnosed with any stage of lung cancer, your doctor will likely request tests to check for biomarkers.

There are two basic types of genomic testing for lung cancer. These involve either taking a tissue sample or a blood sample.

A tissue biopsy is the standard procedure by which doctors obtain a sample for genetic testing. However, if your doctor is planning to surgical remove the cancer regardless of its genetic makeup, a sample of the surgically removed tumor will be saved after the operation for analysis.

Increasingly, doctors will order a liquid biopsy in addition to a tissue biopsy. A liquid biopsy is a blood test that checks for cancer cells circulating in the blood and can be used to detect genetic mutations in these cells. There are advantages to the liquid biopsy:

  • Avoids risks of infections, pneumothorax (collapsed lung), or other complications
  • Offers a good alternative if the tumor is in a hard-to-access place
  • Is less invasive
  • Lets doctors easily compare multiple samples over time to see how you are responding to treatment

A Word From Verywell

The ability to understand the molecular profile of lung tumors is an extremely exciting area of research, and it’s likely that new targeted therapies for newly identified mutations will continually be made available as clinical trials pursue more effective options.

If you have been diagnosed with lung cancer, especially lung adenocarcinoma or squamous cell lung cancer, talk to your doctor about genetic testing. If your results show a genetic biomarker, research the treatments available and connect with others who have the same diagnosis. There are many hopeful opportunities for those with these types of cancer, including medications that allow you to manage the cancer for long periods of time as you would a long-term illness like diabetes.

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