Targeted therapy is one of the most important advances in the history of lung cancer treatment. As we know, infinite proliferation of tumor cells is the main destructive force of malignant tumors, and targeted therapy is to skillfully find the engine that causes infinite proliferation of tumors, i.e., mutated genes, and destroy these specific initiating sources through targeted drugs so as to well control tumor growth. Because of the specificity of the treatment mechanism, targeted drugs have shown good control over tumors. For example, the most familiar EGFR-targeted generation drugs, Eressa (gefitinib), Troche (erlotinib), and Kemena (erlotinib), have an efficiency rate of over 70%. About the generation of targeted drugs, there is a detailed introduction in this public issue. Then today I will list several common mutations based on the NCCN (National Comprehensive Cancer Network) guidelines and the table of common mutation gene probabilities in lung cancer, and the currently available listed drugs. EGFR mutations EGFR (English: epidermal growth factor
receptor, abbreviated as EGFR, ErbB-1 or HER1) is a member of the epidermal growth factor receptor (HER) family. This family includes HER1 (erbB1, EGFR), HER2 (erbB2, NEU), HER3 (erbB3) and HER4 (erbB4). the HER family plays important regulatory roles in cellular physiological processes. The mutation frequency of EGFR gene in Asian adenocarcinoma population is 10%-40%, with common mutation sites: exon 19 deletion mutation, exon 21 L858R point mutation and exon 18 and 20 mutation, etc. The emergence of the first generation of ERSA, Troche and Kemena targets created a miracle in the history of lung cancer treatment. Afatinib, a dual-target inhibitor targeting EGFR and HER2, is a strong inhibitor of second-generation irreversible inhibitors, and its efficacy is certain, but there are relatively more adverse reactions in the country. The second generation of drug treatment in about a year will appear to varying degrees of resistance, in the study of resistance mechanisms found the secondary mutation of T790M, for which the third generation of EGFR-TKI inhibitor AZD9291 is also popular, forming the current three generations of EGR-TKI treatment ladder. We also need to recognize that the only targeted drugs listed in China are the first generation of ERSA, Troche, and Kemena, the second generation drug Afatinib is about to be listed, and the third generation drugs are only available in clinical trials, based on the fact that the drugs are not listed in China, and chemotherapy can be administered after disease progression. Second, ALK fusion or rearrangement ALK fusion or rearrangement accounts for 5%-10% in lung adenocarcinoma, and its common fusion mode is EML4-ALK. its target generation drug is crizotinib which is available in China and can produce 74% efficiency. The patients who use it for a long time will also develop drug resistance at a median time of 1-2 years, i.e., mutation of ALK gatekeeper gene occurs leading to secondary drug resistance, thus prompting the emergence of second and even third generation drugs, and also forming a three-step ladder of ALK therapy, but there is only one ALK-targeted drug listed in China, crizotinib, and chemotherapy is still the choice after ALK resistance. Third, the fusion of ROS1 The fusion of ROS1 has a low mutation rate in lung adenocarcinoma, 1.2% – 1.7%, and is commonly found in young, non-smoking, adenocarcinoma and high-grade histopathological type patients. This gene fusion is similar to ALK and has a clear tumor formation driver and better clinical efficacy. Therefore, the 2017.2 edition of the NCCN guidelines mentions ROS1 for the first time in the routine testing of lung adenocarcinoma, establishing a specific clinical treatment pathway for this patient group. For patients with positive ROS1 rearrangement, first-line primary treatment with crizotinib is recommended with an efficiency of up to 72% , time to resistance of 19.2
After disease progression, chemotherapy or immunotherapy with PD-1 can be administered. There are several other mutated genes associated with lung cancer, so I will not list them one by one and give you a chart to see the drugs corresponding to these genes. At present, the treatment of lung cancer has reached the era of individualization. When each lung cancer patient is seen, it is more important to make a specific category division, and those who are suitable for targeted therapy should still be actively treated with targeted therapy in terms of long-term survival time and quality of patients. It is believed that more driver genes and drugs will be discovered and developed to add bricks to the road of targeted therapy for lung cancer, and we also believe that more drugs will be listed in China to bring gospel to patients.