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As researchers have learned more about the changes in non-small cell lung cancer (NSCLC) cells that help them grow, they have developed drugs to specifically target these changes.
Targeted drugs work differently from standard chemotherapy (chemo) drugs. They sometimes work when chemo drugs don’t, and they often have different side effects. At this time, targeted drugs are most often used for advanced lung cancers, either along with chemo or by themselves.
How they work (mechanism of action): For tumors to grow, they need to form new blood vessels to keep them nourished. This process is called angiogenesis. Angiogenesis inhibitors help stop the formation of new blood vessels. These inhibitors are generally monoclonal antibodies (lab-made versions of a specific immune system protein) that target vascular the endothelial growth factor (VEGF), a protein that helps new blood vessels to form, called VEGF inhibitors.
Examples of VEGF inhibitors:
Side effects of angiogenesis inhibitors:
Because of the risks of bleeding, these drugs often aren’t used in people who are coughing up blood or who are taking drugs called blood thinners. The risk of serious bleeding in the lungs is higher in patients with the squamous cell type of NSCLC, which is why current guidelines do not recommend using bevacizumab in people with this type of lung cancer.
How they work (mechanism of action): In some NSCLCs, the cancer cells have changes in the KRAS gene that cause them to make an abnormal form of the KRAS protein. This abnormal protein helps the cancer cells grow and spread. About 1 in 8 people with NSCLC have a specific type of KRAS gene change called a KRAS G12C mutation. KRAS inhibitors attach to the KRAS G12C protein, which helps keep cancer cells from growing.
These drugs are taken as pills, typically once or twice a day.
NSCLCs with this mutation are often resistant to other targeted drugs, such as EGFR inhibitors (see below).
Examples of KRAS inhibitors:
Side effects of KRAS inhibitors:
How they work (mechanism of action): Epidermal growth factor receptor (EGFR) is a protein on the surface of cells. It normally helps the cells grow and divide. Sometimes NSCLC cells have too much EGFR, which makes them grow faster. Drugs called EGFR inhibitors can block the signal from EGFR that tells the cancer cells to grow. Some of these drugs are often used to treat advanced NSCLCs that have certain mutations in the EGFR gene, although osimertinib can also be used as an adjuvant (additional) treatment after surgery for some earlier-stage lung cancers.
Examples of EGFR inhibitors:
Side effects of EGFR inhibitors:
How they work (mechanism of action): About 5% of NSCLCs have a rearrangement in a gene called ALK. This change is often seen in people who don’t smoke (or who are light smokers), who are younger, and who have the adenocarcinoma subtype of NSCLC. The ALK gene rearrangement produces an abnormal ALK protein that causes the cells to grow and spread. Drugs that inhibit this ALK protein are called ALK inhibitors and are taken as an oral pill.
Examples of ALK inhibitors:
Side effects of ALK inhibitors:
How they work (mechanism of action): About 1% to 2% of NSCLCs have a rearrangement in a gene called ROS1. This change is most often seen in people who have the adenocarcinoma subtype of NSCLC and whose tumors are also negative for ALK, KRAS and EGFR mutations. The ROS1 gene rearrangement is similar to the ALK gene rearrangement, and some drugs can work on cells with either ALK or ROS1 gene changes. These drugs, called ROS1 inhibitors, can often shrink tumors in people whose advanced lung cancers have a ROS1 gene change. They are taken as a pill.
Examples of ROS1 inhibitors:
Side effects of ROS1 inhibitors:
How they work (mechanism of action): In some NSCLCs, the cells have changes in the BRAF gene. Cells with these changes make an altered BRAF protein that helps them grow. Some drugs target this and related proteins.
These drugs are taken as pills or capsules each day.
Examples of BRAF inhibitors:
Side effects of BRAF inhibitors:
How they work (mechanism of action): In a small percentage of NSCLCs, the tumor cells have rearrangement in the RET gene that cause them to make an abnormal form of the RET protein. This abnormal protein helps the tumor cells grow. Drugs known as RET inhibitors can be used to treat advanced NSCLC with the RET rearrangement.
These drugs are taken by mouth as capsules, typically once or twice a day.
Examples of RET inhibitors:
Side effects of RET inhibitors:
How they work (mechanism of action): In some NSCLCs, cancer cells have changes in the MET gene, called a MET exon 14 skipping mutation, that cause them to make an abnormal form of the MET protein. This abnormal protein helps the cancer cells grow and spread. Drugs called MET inhibitors can be used to treat metastatic NSCLC if the cancer cells have certain types of MET gene changes, by attacking the MET protein. They are taken as a pill once or twice a day.
Examples of MET inhibitors:
Side effects of MET inhibitors:
How they work (mechanism of action): In a small percentage of NSCLCs, the cancer cells have certain changes in the HER2 (ERBB2) gene that help them grow. HER2-directed drugs can be used to treat metastatic NSCLC if the cancer cells have certain types of HER2 gene changes. These drugs are infused into a vein (IV). They are typically given once every few weeks.
Examples of HER2 inhibitors:
Side effects of HER2 inhibitors:
How they work (mechanism of action): A very small number of NSCLCs have changes in one of the NTRK genes, called NTRK gene fusions. Cells with these gene changes make abnormal TRK proteins, which can lead to abnormal cell growth and cancer. TRK inhibitors target and disable the proteins made by the NTRK genes.
These drugs are taken as pills, once or twice daily.
Examples of TRK inhibitors:
Side effects of NTRK inhibitors:
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Last Revised: November 22, 2023