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These mutations can cause cells to grow and divide uncontrollably, resulting in cancer. Researchers have identified several gene mutations associated with non-small cell lung cancer (NSCLC). Some of the genes that have mutations include TP53, EGFR, KRAS, ALK, ROS1, BRAF, MET, RET, and NTRK. Oncogenes control when cells divide, grow, and continue to live. Tumor suppressor genes, on the other hand, control the division of cells and trigger cells to die. Certain mutations can “turn on” oncogenes and “turn off” tumor suppressor genes. The changes can cause cells to grow out of control and form tumors. In lung cancer, these mutations are not usually heritable. Instead, these mutations are acquired, meaning that they occur during a person’s lifetime. Some acquired mutations may be due to exposure to chemicals that cause cancer, such as those present in tobacco smoke. However, some genetic mutations can occur randomly without an obvious outside cause. What are genotype-targeted therapies Targeted therapies are treatments that hone in on genetic mutations that cause cancer. By identifying mutations associated with lung cancer, researchers have been able to develop treatments to target specific mutations. These treatments can turn off, or block, the signals that encourage the growth and division of cells, stopping cells from living longer than they should and thereby preventing cancer growth. The most common forms of targeted therapies fall into two categories:Monoclonal antibodies: These block specific targets on the outside of cancer cells. They can also send toxic substances directly to a cancer cell. This helps chemotherapy and radiation therapy reach cancer cells.Small molecule drugs: These work by blocking signals that encourage cancer cells to divide, grow, and spread. One form of this therapy uses angiogenesis inhibitors. These stop the formation of new blood vessels around tumors, starving them of the nutrients that they need. A doctor may use targeted therapies alone or in combination with traditional treatments, such as chemotherapy, radiation therapy, and surgery. In some cases, targeted therapies are effective when chemotherapy is not. Available genotype-targeted drug therapies There are various targeted drug therapies for NSCLC, including: Angiogenesis inhibitors These drugs block the growth of new blood vessels surrounding tumors. This, in turn, starves the tumors of nutrients. Drugs in this category include bevacizumab (Avastin) and ramucirumab (Cyramza). Drugs targeting ROS1 gene mutations These drugs can shrink tumors in people who have advanced lung cancer with a ROS1 gene mutation. Drugs in this category include:crizotinib (Xalkori)ceritinib (Zykadia)lorlatinib (Lorbrena)entrectinib (Rozlytrek) Drugs targeting EGFR gene mutations These drugs are called epidermal growth factor receptor (EGFR) inhibitors, and they work by blocking signals that encourage cell growth. Drugs in this category include:erlotinib (Tarceva)afatinib (Gilotrif)gefitinib (Iressa)osimertinib (Tagrisso)dacomitinib (Vizimpro) In many cases, these drugs can shrink tumors for at least several months. However, in the majority of cases, they eventually stop working. This is often due to further genetic mutations, including a mutation called T790M, against which only Tagrisso is effective. In cases of advanced squamous cell NSCLC, the first-line treatment is necitumumab (Portrazza). One of the rarer types of EGFR mutations, Exon 20, does not respond well to most treatments. Doctors may treat cancer associated with this mutation with amivantamab (Rybrevant) or mobocertinib (Exkivity), along with chemotherapy and immunotherapy medications. Drugs targeting ALK gene mutations This group of drugs can shrink tumors in people with advanced lung cancer with an ALK genetic mutation. A doctor may recommend these drugs instead of chemotherapy or after chemotherapy has stopped working. Drugs in this category include:XalkoriZykadiaalectinib (Alecensa)brigatinib (Alunbrig)Lorbrena Drugs targeting BRAF gene mutations Healthcare professionals use these drugs to treat metastatic NSCLC that involves a BRAF gene mutation. Drugs in this category include dabrafenib (Tafinlar) and trametinib (Mekinist). Drugs targeting NTRK gene mutations These drugs work by targeting and disabling proteins that NTRK genes make. Drugs in this category include larotrectinib (Vitrakvi) and Rozlytrek. Drugs targeting MET gene mutations Known as MET inhibitors, these drugs attack the MET protein, which helps cells grow and spread. Drugs in this category include capmatinib (Tabrecta) and tepotinib (Tepmetko). Drugs targeting RET genetic mutations These drugs, which are called RET inhibitors, work by attacking the RET protein. Drugs in this category include selpercatinib (Retevmo) and pralsetinib (Gavreto). Side effects of targeted drug therapies The side effects vary depending on the medication. Common side effects of targeted therapies for lung cancer include:nauseadiarrheahigh blood pressurefatigueskin rashesloss of appetiteconstipationmouth soreschanges to vision The future of lung cancer treatment Targeted therapies have changed the treatment of NSCLC. A 2020 study found that a decrease in mortality among people with NSCLC corresponded with the approval of targeted therapies. This is a rapidly growing field of research, and scientists are working continuously to identify new targets and create new therapies. Right now, clinical trials are taking place around the world to examine new targeted therapies and immunotherapies. These trials are investigating the role of immune monotherapies, combination immunotherapies, and treatments that combine targeted therapies with immunotherapies. Targeted therapies such as these can provide hope to people with lung cancer who may otherwise have limited treatment options. Frequently asked questions Below, we answer some commonly asked questions about targeted therapy for lung cancer. What is the success rate of targeted therapy for lung cancer According to 2020 research, the rate of treatment success for medications targeting the EGFR, ALK, ROS1, and BRAF gene mutations is within the range of 50–80%. The use of such medications can almost double median overall survival. How long does targeted therapy last for lung cancer In clinical trials, doctors continue target therapy for the participants until either their cancer progresses or the side effects from the medications become too great. Other research confirms that doctors administer most targeted therapy drugs for as long as they help extend a person’s life span. Therapy typically stops if toxicity becomes too significant. Therefore, the duration of targeted therapy for lung cancer varies among individuals. Summary Several genetic mutations are associated with lung cancer. Identifying these mutations in people with NSCLC can help doctors find the best treatment for each individual. These advances in treatment can help improve outcomes and pave the way for future therapies. 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