It is due to the discovery of molecular markers that the treatment of lung cancer has entered the era of individualization, and as the research continues, more and more patients will enjoy the fruits of individualized treatment, and the miracle of lung cancer transformation into a chronic disease is becoming a reality. Research progress of molecular markers for EGFR targeted therapy Among the targeted therapies for lung cancer, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are the most widely used. IPASS and other studies have confirmed the correlation between EGFR mutation detection and targeted therapy, and the concept that EGFR mutation detection should be performed before using EGFR-TKI has gained popularity. gene mutations include two main types: exon 19 deletion and exon 21 L858R point mutation. What is the relationship between EGFR gene copy number amplification and EGFR mutations in predicting the efficacy of EGFR-TKI? The data presented in the IPASS study at this year’s Lung Cancer Congress provide answers to this question. A subgroup analysis of patients with EGFR mutations showed that patients with EGFR exon 19 deletions had a slight advantage in outcome over those with EGFR exon 21 point mutations, with the former also outperforming the latter in terms of symptom improvement. Post hoc analysis showed that EGFR gene copy number amplification was predictive of EGFR-TKI efficacy because the group included a large number of patients with EGFR mutations. Detection of EGFR mutations should be the main focus when performing EGFR-TKI efficacy prediction in the future. The KRAS gene is a negative predictor of EGFR-targeted therapy, yet neither the FLEX nor SATURN studies confirmed it as an efficacy predictor, contradicting previous reports. A congress report this year is an important reference to explain this issue. Junichi from USA reported the relationship between KRAS mutations, copy number amplification and KRAS biological activity and clinical efficacy. By examining KRAS mutation, copy number amplification and KRAS activity in 83 cell lines and 333 lung adenocarcinoma cases, it was found that 15% of patients had only KRAS mutation, 5% had both mutation and copy number amplification, 5% had only copy number amplification, and the remaining 75% had neither mutation nor copy number amplification. The KRAS protein activity was significantly increased in patients with mutations or gene amplifications, with the higher the number of gene amplifications, and the strongest KRAS protein activity was found in patients with mutations accompanied by gene amplifications. Patients with gene mutations accompanied by gene amplification had the worst clinical prognosis. This study suggests that there is also heterogeneity in patients with KRAS mutations and that this heterogeneity may have an impact on the efficacy of EGFR-TKI. How to simplify EGFR mutation detection is a prominent issue currently faced. Professor Hirsch presented at the congress the application of specific antibodies against EGFR exon 19 or 21 mutations for the detection of genetic mutations in lung cancer patients. The specificity was 99% and sensitivity 92%, as verified by immunohistochemical detection of mutated EGFR protein expression in 340 lung cancer tissues and then by gene sequencing. This result is alarming, but has yet to be validated in a multicenter, large-scale population. The efficacy of the drug depends on the changes in the tumor genome on the one hand, and on the genotypic differences in the human body itself on the other. In this regard, the Guangdong Lung Cancer Institute has identified new molecular markers to predict the efficacy of EGFR-TKI, which is mainly metabolized in the liver by cytochrome P450 (CYP) in humans. genetic polymorphism of the locus was strongly associated with the efficacy, which was significantly better in the M1/M1 pure type than in M1/M2 and M2/M2 (P=0.0029). This result is the conclusion of a retrospective study and needs further validation by prospective studies. Progress of molecular markers for individualized chemotherapy Due to the rapid development of pharmacogenomics, molecular markers for traditional chemotherapeutic drugs have been discovered and clinical trials guided by them continue to give surprising results, driving traditional chemotherapy into the era of individualized chemotherapy. In his presentation on the first day, Prof. Scagliotti summarized the 8 most commonly used molecular markers for chemotherapy in lung cancer (see table). Due to the widespread use of pemetrexed in first-line, second-line and maintenance therapy, clinical studies using thymidylate synthase (TS) as a molecular marker are increasing. in the subsequent session presentation, Prof. Scagliotti pointed out that it is the mRNA expression of TS, but not the immunohistochemical detection of the protein, that is strongly associated with efficacy, and he is leading a phase III multicenter randomized clinical controlled study (ITACA) to look at the guiding role of ERCC1, RRM1 and TS on chemotherapy.