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. If treatable mutations are identified by lung cancer genetic testing, your oncologist can use that information to prescribe medications that target your genetic abnormalities specifically.

Among the many benefits of targeted therapies is that they can, in various ways, block what is essentially feeding your cancer cells and allowing them to proliferate—without harming healthy cells. This is different for everyone, even those with the same type of lung cancer.

Genetic testing figures out what is behind your cancer and it is now a routine part of lung cancer care.

Scientist conducting the process of Polymerase chain reaction (PCR) to amplify DNA by using a thermocycler to create samples
Monty Rakusen / Getty Images

The Role of Genetics in Lung Cancer

Lung cancer occurs when cells in the lungs multiply uncontrollably due to genetic mutations. When a gene is exposed to toxins in the environment, or when an error occurs in cell division, a mutation (change) may occur.

All genes are made up of variable sequences of four amino acids (called bases)—adenine, tyrosine, cytosine, and guanine. In some cases, a mutation means 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.

The two main types of mutations that can lead to cancer are driver mutations and passenger mutations. Driver genes have a direct role in the process by which cancer begins, known as oncogenesis. After initiating the cancer, these mutated genes literally fuel 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.

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.

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 non-small cell lung cancer (NSCLC), which accounts for about 80% 85% of lung cancers. Non-small cell lung cancer tends to grow slower than small lung cell cancer (SCLC), an aggressive form that is categorized by the small size of the cancer cells when examined under a microscope.

Less is known about mutations that lead to small cell lung cancer, which accounts for about 10% to 15% of lung cancers and has often spread by the time it is diagnosed. Small lung cell cancer is typically treated with chemotherapy and radiation.

If you’ve been recently diagnosed with non-small cell lung cancer, especially lung adenocarcinoma, genetic testing—also known as molecular profiling or biomarker testing—is a way to identify specific driver mutations that your doctors may be able to target with medications.

Targeted therapies are a form of precision medicine, which means they are selected for you based on precise information about your specific disease. In contrast, with conventional chemotherapy, everyone receives the same drugs, or treatment is only personalized based on sensitivity to certain side effects.

The benefits of targeted therapy are many. Among them:

  • Chemo drugs attack all rapidly dividing cells—cancerous or not—and pose a risk of toxicity. Targeted therapies attack only a particular abnormality present in your cancer cells, which results in significantly less discomfort and a better quality of life during treatment.
  • Some targeted therapies can also block blood vessels from forming and feeding cancer tumors; angiogenesis is the process by which new blood vessels form.
  • 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. Targeted therapy drugs allows for higher response rates and longer progression-free survival rates.

What Genetic Testing Looks For

As much as is known about genetic abnormalities behind lung cancer, this is a relatively new area of medical science. It is assumed, then, that there is more behind cancer cell growth than has yet to be be discovered.

Some of the mutations or alterations in signaling proteins (biomarkers) in lung cancer that are detectable with genetic testing today include:

  • EGFR mutations: Some types of lung cancer overproduce epidermal growth factor receptor (EGFR), a protein involved in cell growth and division. The mutated cells grow too fast. This mutation is common in people with lung cancer who have never smoked.
  • KRAS mutations: A gene that carries instructions for a KRAS protein can be damaged. Instead of the normal protein, cells may make another one that can't regulate growth properly.
  • ALK rearrangements:  About 5% of NSCLCs produce abnormal ALK proteins that cause cancer cells to grow and spread. The abnormal proteins are the result of a fusion of two genes known as anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4).
  • ROS1 rearrangements: About 1% to 2% of NSCLC have a rearrangement in a gene called ROS1. This mutation is similar to the ALK rearrangement in that it's a fusion of ROS1 and another gene and produces an abnormal protein. The ALK and ROS1 rearrangements are so similar that some targeted therapies can work on both conditions.
  • MET amplifications: Some cancers involve a mutation of the mesenchymal epithelial transition (MET) gene, which causes them to produce abnormal proteins and leads to cancer growth and spread.
  • BRAF mutations: Common in smokers, this mutation affects B-Raf proteins and can increase cancer spread.
  • RET mutations: A RET gene on cancer cells changes and forms RET proteins that cause cell proliferation.
  • NTRK mutations: A fusion occurs between a piece of the chromosome containing an NTRK gene and a gene on another chromosome, producing proteins called TRK fusion proteins that cause abnormal cell growth.

For a sense of the impact of discovering one such mutation, drugs that target EGFR mutations result in 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.

Who Should Be Tested?

While there are hereditary lung cancer mutations (also called germline mutations) that are part of your genetic makeup at birth and can be passed down from parent to child, increasing your risk of developing lung cancer, almost all gene mutations related to the disease are acquired. That means they occur because of exposure to carcinogens that damage cell DNA.

These mutations, or somatic mutations, are not present at birth (and do not run in families), meaning anyone can develop them. That is why genetic testing for lung cancer is recommended for all patients.

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

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 conditions: 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.

Lung Cancer Genetic Testing Methods

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.

Tissue Biopsy

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

Many academic cancer centers offer testing on site, or your oncologist can send your tissue sample out to companies and laboratories for comprehensive testing.

Blood Testing

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 a liquid biopsy:

  • Does not pose a risk of infection, pneumothorax (collapsed lung), or other complications associated with tissue biopsy
  • 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

How Results Advise Treatment

Based on the mutations identified, you may be matched with a targeted drug or qualified to enter a clinical trial.

There are several therapies available to target specific mutations that may be involved in lung cancer, and research is ongoing to hopefully develop more.

Your doctor will consider the drug options approved for your specific mutation (if any). For example, while ALK rearrangements may be treated with one of five different drugs approved by the U.S. Food and Drug Administration (FDA), only one drug is approved for MET amplifications.

Identifying mutations can also give your physician additional information—such as how likely it may be for the cancer to recur—that may help with other treatment decisions, such as surgery.

Whether or not you receive a targeted therapy alone or in conjunction with other treatment depends on your case and type of lung cancer.

Resistance to Treatment

Discovering a treatable mutation via genetic testing for lung cancer is encouraging in the sense that it can help form a more tailored treatment plan. But it's important to know that nearly everyone inevitably becomes resistant to currently available targeted treatments with time. 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.

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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