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.