Xiaohong Liu , Wuxuan Mei , Yueru Yao , Changchun Zeng
{"title":"fgfr介导的肺癌信号传导的当前见解和障碍","authors":"Xiaohong Liu , Wuxuan Mei , Yueru Yao , Changchun Zeng","doi":"10.1016/j.ejmech.2025.117897","DOIUrl":null,"url":null,"abstract":"<div><div>Lung cancer remains a significant health challenge, with fibroblast growth factor receptor (FGFR) signaling emerging as a critical player in its pathogenesis. This review examines FGFR's roles in endothelial function, angiogenesis, immune modulation, epithelial-to-mesenchymal transition (EMT), and transdifferentiation in lung cancer. Moreover, FGFR signaling is implicated in resistance to receptor tyrosine kinase (RTK) tyrosine kinase inhibitors (TKIs), particularly those targeting EGFR, ALK, and MET, immune checkpoint inhibitors, and chemotherapies in lung cancer. Furthermore, therapeutic approaches targeting FGFR include multitarget TKIs and selective FGFR inhibitors, which have shown promise in individuals with FGFR alterations. The side effects of FGFR inhibitors in clinical settings and associated management strategies have also been outlined. Additionally, challenges in personalizing FGFR therapies include variable FGFR alterations, diagnostic hurdles, biomarker selection and validation, and trial design intricacies. This comprehensive overview underscores the necessity for innovative approaches to optimize FGFR-targeted therapies in lung cancer treatment.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117897"},"PeriodicalIF":5.9000,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Current insights and barriers in FGFR-mediated signaling in lung cancer\",\"authors\":\"Xiaohong Liu , Wuxuan Mei , Yueru Yao , Changchun Zeng\",\"doi\":\"10.1016/j.ejmech.2025.117897\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Lung cancer remains a significant health challenge, with fibroblast growth factor receptor (FGFR) signaling emerging as a critical player in its pathogenesis. This review examines FGFR's roles in endothelial function, angiogenesis, immune modulation, epithelial-to-mesenchymal transition (EMT), and transdifferentiation in lung cancer. Moreover, FGFR signaling is implicated in resistance to receptor tyrosine kinase (RTK) tyrosine kinase inhibitors (TKIs), particularly those targeting EGFR, ALK, and MET, immune checkpoint inhibitors, and chemotherapies in lung cancer. Furthermore, therapeutic approaches targeting FGFR include multitarget TKIs and selective FGFR inhibitors, which have shown promise in individuals with FGFR alterations. The side effects of FGFR inhibitors in clinical settings and associated management strategies have also been outlined. Additionally, challenges in personalizing FGFR therapies include variable FGFR alterations, diagnostic hurdles, biomarker selection and validation, and trial design intricacies. This comprehensive overview underscores the necessity for innovative approaches to optimize FGFR-targeted therapies in lung cancer treatment.</div></div>\",\"PeriodicalId\":314,\"journal\":{\"name\":\"European Journal of Medicinal Chemistry\",\"volume\":\"296 \",\"pages\":\"Article 117897\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2025-06-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0223523425006622\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0223523425006622","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Current insights and barriers in FGFR-mediated signaling in lung cancer
Lung cancer remains a significant health challenge, with fibroblast growth factor receptor (FGFR) signaling emerging as a critical player in its pathogenesis. This review examines FGFR's roles in endothelial function, angiogenesis, immune modulation, epithelial-to-mesenchymal transition (EMT), and transdifferentiation in lung cancer. Moreover, FGFR signaling is implicated in resistance to receptor tyrosine kinase (RTK) tyrosine kinase inhibitors (TKIs), particularly those targeting EGFR, ALK, and MET, immune checkpoint inhibitors, and chemotherapies in lung cancer. Furthermore, therapeutic approaches targeting FGFR include multitarget TKIs and selective FGFR inhibitors, which have shown promise in individuals with FGFR alterations. The side effects of FGFR inhibitors in clinical settings and associated management strategies have also been outlined. Additionally, challenges in personalizing FGFR therapies include variable FGFR alterations, diagnostic hurdles, biomarker selection and validation, and trial design intricacies. This comprehensive overview underscores the necessity for innovative approaches to optimize FGFR-targeted therapies in lung cancer treatment.
期刊介绍:
The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers.
A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.