EGFR exon 20 insertion mutation in non-small cell lung cancer: classification and clinical treatment research / 药学学报

In recent years, targeted therapy has become the standard treatment for advanced non-small cell lung cancer (NSCLC), but this treatment method has very limited effect on patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation. This insertion mutation is the third most common mutation in EGFR. It shrinks the drug binding pocket and gives tumors inherent resistance to available EGFR tyrosine kinase inhibitors (TKIs), resulting in the limited efficiency of the first and second generation of EGFR tyrosine. So far, no targeted therapy has been approved for NSCLC patients with EGFR exon 20 insertion mutations, and there are still no drugs that have met clinical needs. In this case, new treatment strategies using new EGFR TKIs or bispecific antibodies may establish new treatment standards for these patients in the future. In this review, we will summarize all relevant exon 20 insertions reported so far on the structure of EGFR and its influence on EGFR inhibitor sensitivity, as well as the treatment strategies of exon 20 insertions in NSCLC patients, hoping to be a clinical treatment for reference.

Studies and Progress of EGFR exon 20 Insertion Mutation in Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer has the highest morbidity and mortality among malignant tumors worldwidely. Targeted therapy related to non-small cell lung cancer (NSCLC) is the research hotspot in recent year. The emergence of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has brought a huge change in the treatment of patients with EGFR mutation. The patients with EGFR exon20 insertion are specific cohort in NSCLC. Reviewing the clinical researches to EGFR exon20 insertion mutation positive NSCLC, as well as summarizing character, testing methods and treatment, will provide a help for clinical application, bringing more benefits for patients at the same time.

Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie

P-glycoprotein (P-gp) is encoded by the ABCB1 gene and acts as an efflux pump for xenobiotics. In the Border Collie, a nonsense mutation caused by a 4-base pair deletion in the ABCB1 gene is associated with a premature stop to P-gp synthesis. In this study, we examined the full-length coding sequence of the ABCB1 gene in an ivermectin-sensitive Border Collie that lacked the aforementioned deletion mutation. The sequence was compared to the corresponding sequences of a wild-type Beagle and seven ivermectin-tolerant family members of the Border Collie. When compared to the wild-type Beagle sequence, that of the ivermectin-sensitive Border Collie was found to have one insertion mutation and eight single nucleotide polymorphisms (SNPs) in the coding sequence of the ABCB1 gene. While the eight SNPs were also found in the family members' sequences, the insertion mutation was found only in the ivermectin-sensitive dog. These results suggest the possibility that the SNPs are species-specific features of the ABCB1 gene in Border Collies, and that the insertion mutation may be related to ivermectin intolerance.