Lung cancer targeted therapy guide | List of targets and corresponding drugs
Lung adenocarcinoma is the most common type of non-small cell lung cancer (NSCLC). With medical advances, targeted therapy has become an important treatment option for advanced lung adenocarcinoma. This article will help you understand what targeted therapy is, common gene mutation targets, and corresponding targeted drugs.
🎯 What is targeted therapy?
Targeted therapy is a type of treatment that targets specific gene mutations or abnormal proteins in cancer cells. Through genetic testing, we can identify specific mutations in tumor cells and use corresponding drugs for treatment, which can improve the efficacy and reduce damage to normal cells.
🧬 Common gene mutation targets and corresponding drugs
Target 1: EGFR (epidermal growth factor receptor) mutation
EGFR mutation is the most common genetic alteration in Asian lung adenocarcinoma patients, accounting for approximately 50% of all patients. The corresponding targeted drugs include:
First generation drugs. It is the earliest developed EGFR inhibitor and has good efficacy against common mutations such as Exon 19 deletion and Exon 21 L858R. but After a period of use, some patients develop resistance (most commonly T790M mutation)
2. Afatinib (Gilotrif)
Second generation drugs. It is more effective than the first-generation drugs and is also effective against some uncommon mutations. However, due to its strong effect, it will also affect normal cells, and the side effects (such as rash and diarrhea) are more obvious. In addition, T790M resistance mutation may still occur
Third generation drugs. It can target the T790M drug-resistant mutation (which the first and second generations cannot deal with), and is also effective against the original common mutations. It has strong penetrating power and can control brain metastasis. It has become the most mainstream EGFR targeted drug
Specific mutation drugs. A small number of patients will have exon 20 insertion mutations, which are poorly responsive to traditional EGFR targeted drugs. Mobocitinib is the first oral targeted drug designed specifically for EGFR Exon 20 insertion mutations
Target 2: ALK (anaplastic lymphoma kinase) rearrangement
Approximately 3-5% of lung adenocarcinoma patients have ALK gene rearrangement. The corresponding targeted drugs include:
First generation drugs. It is the first drug approved for the treatment of ALK-positive non-small cell lung cancer and also has the function of inhibiting ROS1 rearrangement. The disadvantage is that the drug cannot penetrate the brain (central nervous system) and drug resistance is likely to occur. The average disease control time is about 8-10 months
2. Ceritinib (Zykadia)
Second generation drugs. It is effective against a variety of ALK resistance mutations, has good brain penetration ability, and can treat or prevent brain metastases. It is usually used for patients who have failed to respond to crizotinib treatment and is often used as a first-line drug.
Third generation drugs. It is the most powerful ALK inhibitor currently available, capable of targeting a variety of ALK resistance mutations (including the G1202R mutation). It has the strongest penetrating power and can control central nervous system metastasis. It is usually used when resistance develops after treatment with second-generation drugs. It has also been approved as a first-line treatment option in some countries
Target 3: MET gene abnormality
Abnormalities of the MET gene include MET exon 14 skipping mutations and MET amplification mutations .
For MET exon 14 skipping mutations, the first-choice drug is capmatinib (Tabrecta) . Capmatinib has been approved by the FDA for first-line and second-line treatment
There is currently no globally approved first-choice drug for MET amplification mutations, but the most commonly used in clinical practice is Crizotinib (Xalkori) and cabozantinib (Cabometyx )
Target 4: ROS1 rearrangement
ROS1 rearrangement occurs in approximately 1-2% of lung adenocarcinoma patients. The corresponding targeted drug is crizotinib (Xalkori)
Target 5: RET gene rearrangement
RET gene rearrangement occurs in approximately 1-2% of lung adenocarcinoma patients. The corresponding targeted drug is Celpatinib (Retevmo)
Target 6: KRAS mutation
In the past, KRAS was considered an "undestinable mutation", but now there are drugs specifically targeting the G12C mutation. The corresponding targeted drug is Sotolacib (Lumakras)
Target 7: BRAF V600E mutation
BRAF V600E mutation occurs in approximately 1-2% of lung adenocarcinoma patients. The corresponding targeted drugs include dabrafenib ( Tafinlar and trametinib (Mekinist)
🧪 Why is genetic testing important?
Before starting targeted therapy, genetic testing of tumor tissue or blood can be performed to find out whether the above gene mutations exist. This helps physicians select the most appropriate targeted drug, improve treatment efficacy and reduce unnecessary side effects.
💡 Summary
Targeted therapy has brought new hope to patients with lung adenocarcinoma, but it is not suitable for all patients. Through genetic testing, we can identify the specific mutations of the tumor and choose the most appropriate treatment plan. Patients are advised to discuss with their doctors to understand their genetic condition and develop a personalized treatment plan.
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