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Treating Non-Small Cell Lung Cancer

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Genetic Subtypes of Stage 4 Lung Cancer

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Stage 4 lung cancer, or metastatic lung cancer, refers to cancer that has spread beyond your lungs to other parts of your body. Historically, stage 4 lung cancer has been challenging to treat using traditional cancer therapies, such as chemotherapy, radiation, and surgery. But more recently, a newer method of treating lung cancer, called personalized medicine, has emerged. This involves examining your cancer cells for certain changes in its DNA, also known as genetic mutations, and classifying your cancer into a genetic subtype based on which mutations are present. Your genetic subtype of lung cancer can help guide treatment decisions. Here’s how it works.

Is lung cancer caused by genetics?

Lung cancer is generally not an “inherited” condition, meaning it’s usually not passed down through families like some other diseases. In a small number of cases, certain inherited gene mutations can place you at an increased risk of developing cancer in your lifetime.

Instead, lung cancer usually develops from genetic mutations that are acquired throughout your life. This often occurs from things that cause damage to your lungs, like smoking or exposure to harmful chemicals. As a result of these changes, the cells in your lungs may grow abnormally and become cancerous.

What are some common genetic subtypes of lung cancer?

Researchers have been able to identify several specific gene mutations that help lung cancer cells grow. If you have lung cancer, particularly non-small cell lung cancer (NSCLC), your cancer may be screened for the following genetic mutations:

  • EGFR mutation: Epidermal growth factor receptor (EFGR) is a protein that plays a role in how your cells grow and divide. A mutation in the EGFR gene can cause cells to grow out of control. This mutation is found in 10 to 35% of cases of NSCLC and is often present in non-smokers who develop lung cancer.
  • KRAS mutation: About 25% of people with non-small cell lung cancer have a mutation in this gene, which helps regulate cell growth and division.
  • ALK rearrangement: In this mutation, the ALK gene attaches to another gene, creating a protein that causes uncontrolled cell growth. Around 5% of people with NSCLC have this mutation.

There are many other known gene mutations associated with lung cancer, such as the ROS1, BRAF, MET, NTRK, and RET gene changes, that affect a smaller subset of individuals. Based on your type and stage of lung cancer, your doctor will determine which screening tests are most appropriate.

How does identifying genetic subtypes of stage 4 lung cancer inform treatment?

Since researchers are now able to pinpoint different genetic changes that help lung cancer cells spread, they have worked to develop treatments that block those specific changes. These are known as targeted therapies and are used to slow or stop cancer growth without harming healthy cells. 

Many targeted therapies have been approved for gene mutations associated with lung cancer. For example, some people with the EGFR mutation may be treated with a drug known as a tyrosine kinase inhibitor (TKI). These drugs block the signal from the EGFR protein that makes lung cancer cells grow. Some targeted drugs are used on their own, while others are combined with other cancer treatments.

It’s not uncommon for stage 4 lung cancer to become resistant to treatment over time. Depending on your tumor genotype, your doctor may recommend trying a different targeted therapy or enrolling you in a clinical trial to voluntarily study a treatment in development. New gene mutations and treatments that target them are also likely to be discovered as time goes on. Talk to your doctor about what options are available to you.

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Medical Reviewer: William C. Lloyd III, MD, FACS
Last Review Date: 2021 Sep 28
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THIS TOOL DOES NOT PROVIDE MEDICAL ADVICE. It is intended for informational purposes only. It is not a substitute for professional medical advice, diagnosis or treatment. Never ignore professional medical advice in seeking treatment because of something you have read on the site. If you think you may have a medical emergency, immediately call your doctor or dial 911.
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