5 Lung Cancer Mutations and Treatments That Target Them | MyLungCancerTeam

Connect with others who understand.

sign up Log in
Resources
About MyLungCancerTeam
Powered By

5 Lung Cancer Mutations and Treatments That Target Them

Medically reviewed by Leonora Valdez, M.D.
Written by Emily Wagner, M.S.
Updated on May 20, 2024

Like all cancers, lung cancer is caused by mutations, or genetic changes, in DNA. Mutations in genes involving cell growth can lead to cancer, so these genes are considered oncogenes. Mutations in oncogenes result in faulty proteins that are always active and tell a lung cell to grow and divide continually. Cancer develops when this growth becomes uncontrolled.

Mutations can also be found in tumor suppressor genes (TSGs, also known as antioncogenes), which are responsible for controlling cell growth. When mutations occur in TSGs, the body loses its ability to keep cell growth under control, which can result in cancer.

Oncogenes and TSGs work in balance to keep cells from dividing too quickly or too slowly. For example, oncogenes can be compared to the gas pedal in a car, and TSGs are the brakes. In cancer, the cells accelerate on the gas with no brakes, leading to uncontrolled growth and division, and, as a result, tumors.

Finding the Right Mutations To Treat

There are two main forms of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Each form is classified by the types of lung cells affected. SCLC accounts for around 15 percent of lung cancer cases, and NSCLC makes up the other 85 percent.

NSCLC can be broken down into three subtypes: lung adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. SCLC can be broken down into two subtypes: small cell carcinoma (oat cell cancer) and combined small cell carcinoma.

Lung Cancer Mutations by Type

Lung cancer most often develops as a result of somatic mutations. These mutations cannot be passed down through family. In rare cases, lung cancer can be caused by germline mutations, which can be passed down through family members.

NSCLC commonly has mutations in a group of proteins known as receptor tyrosine kinases (RTKs) that signal cells to grow. Healthy cells can shut down RTKs once they have signaled. However, in cancer cells, this signaling does not stop, and the cells grow uncontrollably. Examples of RTKs that play a role in NSCLC include epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK).

SCLC commonly has mutations in the TP53 gene but rarely has other mutations. Having few mutations can make SCLC difficult to treat because it can’t usually be treated with targeted therapies.

Identifying Mutations in Lung Cancer

Oncologists order a lung biopsy to diagnose lung cancer and test for genetic mutations. Needle biopsies remove tissue samples from lung tumors, which are then prepared for molecular testing.

In the lab, DNA sequencing tests are used to look for mutations in genes commonly associated with lung cancer.

Targeted Therapy for Lung Cancer

If there are targeted therapies available for the mutations in your lung cancer, your doctor may prescribe these. Targeted therapies include tyrosine kinase inhibitors (TKIs), which work by blocking the function of RTKs (EGFR, ALK). Targeted therapies can be used as first-line lung cancer treatment. In some cases, targeted therapy can be combined with chemotherapy for better results.

Here are some of the mutations seen in lung cancer and the targeted therapies directed against them.

1. EGFR Mutations

EGFR is a growth-signaling protein found on the outside of cells. EGFR gene mutations are the second most common genetic mutation found in NSCLC, accounting for about 10 percent to 20 percent of cases in white people and at least 50 percent of cases in the Asian population. EGFR mutations are more likely to occur in people who don’t smoke.

Targeted Treatments for EGFR Mutations

The following targeted therapies are approved by the U.S. Food and Drug Administration (FDA) for lung cancers containing EGFR mutations:

  • Erlotinib (Tarceva)
  • Gefitinib (Iressa)
  • Afatinib (Gilotrif)
  • Dacomitinib (Vizimpro)
  • Osimertinib (Tagrisso)

You can learn more about these medications and other treatments for lung cancer here.

2. ALK Mutations

The ALK gene controls another cell surface protein that signals cell growth. Some studies from the journal Cancers suggest that EML4-ALK mutations occur in 6.7 percent of NSCLC cases.

Targeted Treatments for ALK Mutations

There are several approved therapies to target the ALK mutation, including:

  • Crizotinib (Xalkori)
  • Alectinib (Alecensa)
  • Ceritinib (Zykadia)
  • Lorlatinib (Lorbrena)
  • Brigatinib (Alunbrig)

3. KRAS Mutations

KRAS is a protein that helps send signals inside cells after a growth signal is received. When it is mutated, KRAS is continuously active and cannot be shut off. As a result, it acts as an oncogene and keeps sending signals inside the cell to grow and divide, leading to cancer.

KRAS mutations are found in 20 percent to 25 percent of lung cancers.

Targeted Treatments for KRAS Mutations

The FDA has approved two targeted therapies for lung cancers with the KRAS mutation:

  • Sotorasib (Lumakras)
  • Adagrasib (Krazati)

4. BRAF Mutations

BRAF is a protein known as a kinase. It’s responsible for sending signals inside cells for growth and division. BRAF mutations are found in roughly 4 percent of NSCLC cases, specifically in lung adenocarcinoma.

Targeted Treatments for BRAF Mutations

Targeted treatments for lung cancer with BRAF mutations are known as BRAF inhibitors. BRAF inhibitors include:

  • Dabrafenib (Tafinlar)
  • Encorafenib (Braftovi)
  • Vemurafenib (Zelboraf)

These therapies may be prescribed alone or with another form of targeted therapy called MEK inhibitors, which include:

  • Trametinib (Mekinist)
  • Binimetinib (Mektovi)

5. TP53 Mutations

Tumor protein p53, or TP53, is a gene that encodes for the protein p53. This means that the TP53 gene contains the instructions necessary to make the p53 protein. This protein is found in the nucleus of the cell and helps repair damaged DNA. DNA damage can occur for several reasons, including exposure to radiation, ultraviolet light, and chemicals. Cancer cells can also have damaged DNA because they divide too quickly and cannot repair the DNA.

When healthy cells sense this damage, p53 turns on other genes to help repair the DNA. P53 is considered a TSG and has even been given the nickname “guardian of the genome.” In lung cancer cells, however, p53 is often mutated so it can’t help repair damaged DNA. P53 mutations are almost always found in cases of SCLC but can also occur in NSCLC.

TP53 Mutation Treatments

There aren’t any FDA-approved targeted therapies for people with lung cancer caused by TP53 mutations. However, several promising treatment options are under review in oncology clinical trials — research studies that test new treatments to see if they are safe and effective for people with cancer. Other targeted therapies have been approved for TP53 mutations associated with other conditions. Before doctors can prescribe these therapies for lung cancer, more research is needed to confirm they are safe and effective.

Talk With Others Who Understand

MyLungCancerTeam is the social network for people with lung cancer and their loved ones. On MyLungCancerTeam, more than 12,000 members come together to ask questions, give advice, and share their stories with others who understand life with lung cancer.

When you received your lung cancer diagnosis, did your health care provider explain details about your type of lung cancer and which mutations were found? Did those details figure into your treatment plan? Share your experience in the comments below, or start a conversation by posting on your Activities page.

References
  1. Oncogene — National Cancer Institute
  2. Tumor Suppressor Gene — National Cancer Institute
  3. Lung Cancer — MedlinePlus
  4. Non-Small Cell Lung Cancer Treatment (PDQ) — Health Professional Version — National Cancer Institute
  5. Small Cell Lung Cancer Treatment (PDQ) — Patient Version — National Cancer Institute
  6. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Lung Cancer: History, Epidemiology, and Market Outlook — Cureus
  7. Recent Progress in Mapping the Emerging Landscape of the Small-Cell Lung Cancer Genome — Experimental & Molecular Medicine
  8. Tests for Lung Cancer — American Cancer Society
  9. Biomarker Testing for Cancer Treatment — National Cancer Institute
  10. Tyrosine Kinase Inhibitor — National Cancer Institute
  11. Targeted Drug Therapy for Non-Small Cell Lung Cancer — American Cancer Society
  12. Rare Epidermal Growth Factor in Non-Small Cell Lung Cancer ​​— Seminars in Cancer Biology
  13. Impact of Heavy Smoking on the Benefits From First-Line EGFR-TKI Therapy in Patients With Advanced Lung Adenocarcinoma — Medicine
  14. ALK Gene — MedlinePlus
  15. EML4-ALK Variants: Biological and Molecular Properties, and the Implications for Patients — Cancers
  16. KRAS Gene — MedlinePlus
  17. FDA Approves First Targeted Therapy for Lung Cancer Mutation Previously Considered Resistant to Drug Therapy — U.S. Food and Drug Administration
  18. FDA Grants Accelerated Approval to Adagrasib for KRAS G12C-Mutated NSCLC — U.S. Food and Drug Administration
  19. BRAF Gene — MedlinePlus
  20. BRAF and Lung Cancer — American Lung Association
  21. TP53 Gene — MedlinePlus
  22. Drugs Targeting p53 Mutations With FDA Approval and in Clinical Trials — Cancers
    Updated on May 20, 2024
    All updates must be accompanied by text or a picture.

    We'd love to hear from you! Please share your name and email to post and read comments.

    You'll also get the latest articles directly to your inbox.

    This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
    Leonora Valdez, M.D. received her medical degree from the Autonomous University of Guadalajara before pursuing a fellowship in internal medicine and subsequently in medical oncology at the National Cancer Institute. Learn more about her here.
    Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

    Related Articles

    If you’re an older adult with lung cancer, you might have specific needs related to aging. It’s i...

    8 Facts About Lung Cancer in Older Adults: Treatment Options, Prognosis, and More

    If you’re an older adult with lung cancer, you might have specific needs related to aging. It’s i...
    Doctors and scientists are constantly finding new and better ways to treat lung cancer. In the pa...

    New Lung Cancer Treatments: 8 Advancements in Research

    Doctors and scientists are constantly finding new and better ways to treat lung cancer. In the pa...
    Pneumonectomy is a type of lung cancer surgery. This procedure involves removing the entire lung ...

    Can You Live With One Lung? Recovery, Complications, and More

    Pneumonectomy is a type of lung cancer surgery. This procedure involves removing the entire lung ...
    Some medical procedures are used only in certain cases. For people with severe lung damage, a lun...

    Lung Transplant for Lung Cancer: Is It an Option?

    Some medical procedures are used only in certain cases. For people with severe lung damage, a lun...
    Proton therapy is a type of radiation therapy (also called radiotherapy) that’s being used more f...

    5 Facts About Proton Therapy for Lung Cancer

    Proton therapy is a type of radiation therapy (also called radiotherapy) that’s being used more f...
    Have you noticed a burning, searing, or painful sensation in your nerves after receiving chemothe...

    Scrambler Therapy for Nerve Pain After Chemo: 6 Facts To Know

    Have you noticed a burning, searing, or painful sensation in your nerves after receiving chemothe...

    Recent Articles

    Did you know that a lung abscess can look like lung cancer on an X-ray? Lung abscesses come from ...

    Lung Abscess vs. Lung Cancer: How Do Doctors Tell the Difference?

    Did you know that a lung abscess can look like lung cancer on an X-ray? Lung abscesses come from ...
    If you’ve recently been diagnosed with a Pancoast tumor, you may be wondering what this means for...

    Pancoast Tumors: 6 Facts About Cancer in the Top of the Lung

    If you’ve recently been diagnosed with a Pancoast tumor, you may be wondering what this means for...
    MyHealthTeam does not provide health services, and if you need help, we’d strongly encourage you ...

    Crisis Resources

    MyHealthTeam does not provide health services, and if you need help, we’d strongly encourage you ...
    Loss of appetite is a common symptom of living with lung cancer, and it can also be a side effect...

    Loss of Appetite With Lung Cancer: 13 Tips To Improve Eating

    Loss of appetite is a common symptom of living with lung cancer, and it can also be a side effect...
    Choosing the right hospital for lung cancer treatment is one of the most critical decisions you c...

    Best Hospitals for Lung Cancer Treatment: 7 Features To Look For

    Choosing the right hospital for lung cancer treatment is one of the most critical decisions you c...
    Did you know lung cancers can spread beyond the chest? The term “metastasis” refers to cancer tha...

    When Lung Cancer Spreads to the Adrenal Glands: What To Expect

    Did you know lung cancers can spread beyond the chest? The term “metastasis” refers to cancer tha...
    MyLungCancerTeam My lung cancer Team

    Thank you for subscribing!

    Become a member to get even more:

    sign up for free

    close