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Taking early preventive interventions to manage the challenging issue of acquired resistance to third-generation egfr inhibitors

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2023年第1期1卷 3-10页

作者： Shi-Yong Sun Department of Hematology and Medical Oncology Emory University School of Medicine and Winship Cancer Institute of Emory UniversityAtlantaGA 30322USA

Although the clinical efficacies of third-generation epidermal growth factor receptor(egfr)-tyrosine kinase in-hibitors(TKIs)such as osimertinib in the treatment of non-small cell lung cancer(NSCLC)with egfr-activating mutations are promising,drug-acquired resistance inevitably occurs whether they are used as first-line or second-line treatment.Therefore,managing the acquired resistance to third-generation egfr-TKIs is crucial in the clinic for improving patient survival.Great efforts have been made to develop potentially effective strategies or regimens for the treatment of egfr-mutant NSCLC patients after relapse following these TKIs therapies with the hope that patients will continue to benefit from treatment through overcoming acquired resistance.Although this approach,which aims to overcome drug-acquired resistance,is necessary and important,it is a passive practice.Taking pre-ventive action early before disease progression to manage the unavoidable development of acquired resistance offers an equally important and efficient approach.We strongly believe that early preventive interventions using effective and tolerable combination regimens that interfere with the process of developing acquired resistance may substantially improve the outcomes of egfr-mutant NSCLC treatment with third-generation egfr-TKIs.Thus,this review focuses on discussing the scientific rationale and mechanism-driven strategies for delaying and even preventing the emergence of acquired resistance to third-generation egfr-TKIs,particularly osimertinib.

关键词： Lung cancer Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors(egfr-TKIs) Osimertinib Acquired resistance egfr mutations

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Genetic Polymorphism, Telomere Biology and Non-Small Lung Cancer Risk

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Journal of Genetics and Genomics 2015年第10期42卷 549-561页

作者： Rongrong Wei Frank T.De Vilbiss Wanqing Liu Department of Medicinal Chemistry and Molecular Pharmacology College of Pharmacy Purdue University School of Chemical Engineering Purdue University

Recent genome-wide association studies （GWAS） have identified a number of chromosomal regions associated with the risk of lung cancer. Of these regions, single-nucleotide polymorphisms （SNPs）, especially rs2736100 located in the telomerase reverse transcriptase （TERT） gene show unique and significant association with non-small cell lung cancer （NSCLC） in a few subpopulations including women, nonsmokers, East Asians and those with adenocarcinoma, Recent studies have also linked rs2736100 with a longer telomere length and lung cancer risk. In this review, we seek to summarize the relationship between these factors and to further link the underlying telomere biology to lung cancer etiology. We conclude that genetic alleles combined with environmental （e.g., less-smoking） and physiological factors （gender and age） that confer longer telomere length are strong risk factors for NSCLC. This linkage may be particularly relevant in lung adenocarcinoma driven by epidermal growth factor receptor （egfr） mutations, as these mutations have also been strongly linked to female gender, less-smoking history, adenocarcinoma histology and East Asian ethnicity, By establishing this connection, a strong argument is made for further investigating of the involvement of these entities during the tumorigenesis of NSCLC.

关键词： Telomere Non-small cell lung cancer Cancer risk Polymorphism egfr mutations

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