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Imagine if cancer treatment could be tailored like a custom suit, designed to fit the unique features of a person’s tumor. That’s the promise of targeted therapy. This powerful approach zeroes in on gene changes that drive the growth of lung cancer. Unlike traditional treatment types such as chemotherapy, which affect the whole body, targeted therapies act with more precision to help stop cancer growth at its source.
In this article, we’ll explain how targeted therapy works and when it’s recommended for treating lung cancer.
Targeted therapy is a type of cancer treatment that focuses on specific changes in cancer cells. These changes are often caused by mutations — alterations in the DNA that affect how cells grow and divide. In lung cancer, some of these changes produce abnormal proteins that help cancer grow. Targeted therapy works by finding and blocking these proteins, which stops the cancer cells from growing.
Doctors usually recommend targeted drugs to treat a type of lung cancer called non-small cell lung cancer (NSCLC). Currently, targeted therapies are reserved mostly for advanced cases of NSCLC. Many people on these therapies have tried standard treatments such as chemotherapy and radiation therapy. In some cases, targeted therapies are given with chemotherapy to help shrink tumors. Ongoing studies are looking at whether targeted therapies can also be used in earlier stages of NSCLC.
Targeted therapies identify abnormal proteins on or inside cancer cells. One key group of these proteins is called receptor tyrosine kinases (RTKs). Under normal conditions, RTKs help cells grow in response to specific signals. But in lung cancer, abnormal RTKs may send constant signals — even when they shouldn’t — causing cancer cells to grow out of control. Targeted therapies block these faulty signals, helping to slow or stop cancer growth.
Some cancer cells may have too many copies of the genes that make RTK proteins. This leads to an overproduction of receptors on the cell surface, which in turn sends too many growth signals inside the cell, driving it to grow and divide too fast.
When cells grow and divide uncontrollably, they can accumulate additional mutations in their DNA. Eventually, these mutations may cause cells to become cancerous or make an existing cancer more aggressive.
Researchers have developed targeted therapies called tyrosine kinase inhibitors (TKIs) that block specific RTKs known to be mutated or overactive in lung cancer. By interfering with the receptors' ability to send growth signals, TKIs can help slow cancer progression and shrink tumors.
In some cases of NSCLC, certain RTKs in lung cancer are mutated. These mutated RTKs can become targets for treatment in people whose cancer cells make these proteins. Many NSCLC cases are caused by these mutations, which is why targeted therapies are often recommended.
As part of your lung cancer diagnosis, your cancer cells may be tested for abnormal proteins and gene mutations — a process called biomarker testing. This testing helps identify which targets are present in your lung cancer and guides your care team in selecting targeted therapies that are most likely to be effective.
Epidermal growth factor receptor (EGFR) is an RTK that signals cells to grow and divide when it interacts with epidermal growth factor. About 10 percent to 15 percent of lung cancer cases involve EGFR mutations.
TKIs interrupt the growth signals that EGFR sends inside cells. Some drugs bind permanently to the receptor, which can cause the tumor cells to die. TKIs for EGFR mutations include:
Osimertinib (Tagrisso) is often used when a person’s cancer becomes resistant to earlier-generation EGFR inhibitors. More recently, osimertinib also was approved as a first-line treatment for some people with EGFR-mutated NSCLC. In addition, osimertinib has been shown to improve survival rates when given after surgery (known as adjuvant therapy).
Two drugs have also been developed to treat NSCLC with EGFR mutations. Amivantamab-vmjw (Rybrevant) binds to two RTKs — EGFR and MET — to stop them from signaling to cells. Necitumumab (Portrazza) is given to people with EGFR mutations and advanced squamous cell NSCLC, a specific type.
In 2024, the U.S. Food and Drug Administration (FDA) approved lazertinib (Lazcluze) in combination with amivantamab-vmjw for NSCLC with certain EGFR mutations.
Anaplastic lymphoma kinase (ALK) is another RTK that can be affected in NSCLC. ALK mutations are found in around 5 percent of NSCLC cases. Several TKIs have been developed to stop ALK from signaling cells to grow and divide, including:
More ALK inhibitors are in the pipeline. Neladalkib is currently in clinical trials to find out whether it can work for people who’ve developed resistance to other drugs that target ALK.
BRAF is an enzyme found inside cells that’s responsible for signaling growth and division. BRAF is mutated in around 4 percent of NSCLC cases (most often the V600E mutation) and is most often found in the adenocarcinoma subtype. Targeted therapies for BRAF and other proteins include:
BRAF inhibitors are sometimes combined with another medication that targets a pathway known as MEK. These MEK inhibitors include trametinib (Mekinist) and binimetinib (Mektovi).
Some NSCLC cases involve ROS1 gene mutations, which are similar to ALK mutations. For that reason, many TKIs used to treat ALK mutations can also treat ROS1 mutations and vice versa. These drugs include:
Another ROS1 inhibitor, taletrectinib, is being studied in clinical trials.
KRAS mutations occur in up to 30 percent of NSCLC cases. One specific mutation, KRAS G12C, is found in 40 percent of those. For years, no targeted therapies addressed this mutation, and many researchers thought it could never be treated.
In 2021, the FDA approved the first KRAS inhibitor, sotorasib (Lumakras). This drug targets the mutated form of KRAS while sparing the healthy version. A second KRAS inhibitor, adagrasib (Krazati), was approved in December 2022.
Some TKIs block NTRK, a growth receptor that can be mutated in NSCLC, although this is rare. These drugs include entrectinib, larotrectinib (Vitrakvi), and repotrectinib.
RET is another RTK that’s rarely mutated in NSCLC. Two targeted therapies, pralsetinib (Gavreto) and selpercatinib (Retevmo), have been developed to block the receptor from sending growth signals. Cabozantinib (Cabometyx, Cometriq) may also be used in some cases.
In a small number of NSCLC cases, changes in the HER2 gene help cancer cells grow and divide. HER2 inhibitors, a newer group of targeted therapies, lock on to the HER2 protein on the surface of cancer cells. They’re generally used for metastatic NSCLC (when the cancer has spread to other parts of the body). Examples of HER2-targeted therapies include:
Angiogenesis inhibitors are also used to treat NSCLC. This type of targeted therapy stops new blood vessels from forming around tumors.
A blood supply provides tumors with the oxygen and nutrients they need to grow. Tumors create their own new blood vessels in a process known as angiogenesis. Vascular endothelial growth factor (VEGF) tells cells to produce these new blood vessels.
Targeted therapies were developed to stop this process. Bevacizumab (Avastin) and ramucirumab (Cyramza) are monoclonal antibodies that bind to VEGF and keep it from activating its receptor. By blocking this signal, these drugs reduce the tumor’s blood supply, which can help shrink the tumor.
Like all medications, targeted therapies come with some side effects. Many TKIs have similar side effects because the drugs work the same way and block similar receptors.
Common side effects of targeted therapies used in lung cancer include:
Many side effects can be similar to those caused by other cancer treatments, such as chemotherapy, radiation therapy, or immunotherapy. If you’re receiving more than one type of treatment at the same time, it can be hard to tell which is responsible for specific side effects.
That said, targeted therapies generally have a different side effect profile. Because they’re designed to block specific changes in cancer cells, they tend to spare healthy cells. As a result, they’re less likely to cause certain side effects — such as nausea and vomiting — that are more common with chemotherapy. Thanks to these advances, many people are now able to manage their treatment with fewer side effects and maintain a better quality of life.
MyLungCancerTeam is the social network for people with lung cancer and their loved ones. On MyLungCancerTeam, more than 15,000 members come together to ask questions, give advice, and share their stories with others who understand life with lung cancer.
Have you used targeted therapy to treat your lung cancer? Share your experience in the comments below, or start a conversation by posting on your Activities page.
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I also went threw stereotactic radiation for Stage 1-non-small lung cancer in my left Lung 10 yrs ago. Like you this was my only treatment, my cancer went in remission for 10 yrs. now with a Pet scan… read more
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