Combined treatment with cetuximab and STA9090 has synergistic anticancer effects on human non-small cell lung cancer  

作　　者：Wanjun Lu Lixia Liu Xiang Kang Kangkang Ren Ye Huang Minzhang Cheng Xiaolei Li Fei Xu Xinping Xu 

机构地区：[1]Jiangxi Clinical Research Center for Respiratory Diseases,Jiangxi Institute of Respiratory Disease,Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital,Jiangxi Medical College,Nanchang University,Nanchang 330006,China [2]The First Clinical Medical College,Nanchang University,Nanchang 30006,China [3]Department of Occupational Health and Occupational Medicine,Guangdong Provincial Key Laboratory of Tropical Disease Research,School of Public Health,Southern Medical University,Guangzhou 510515,China [4]Jiangxi Hospital of China-Japan Friendship Hospital,Nanchang 330052,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第7期1022-1033,共12页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of Jiangxi Province,China(Nos.20202ACBL206024 and 20212BAB206034);the Innovative and Entrepreneurial Youth Talents Project of Jiangxi(No.JXSQ2018106040);the Li Ka Shing Foundation LKSF(No.1210669001).

摘　　要：Cetuximab(CET),a human murine chimeric IgG monoclonal antibody and an inhibitor of epidermal growth factor receptor(EGFR),has been shown to be effective in treating various types of cancer.However,its use is hindered by limitations such as resistance development,variability in patient response,side effects,and challenges in biomarker identification.Therefore,CET is often combined with other targeted therapies or chemotherapies to enhance its effectiveness.In this study,we investigate the anticancer effects and underlying mechanisms of the combination of CET,an EGFR inhibitor,and STA9090,an inhibitor of heat shock protein 90(Hsp90),in both in vitro and in vivo models of non-small cell lung cancer(NSCLC).The results demonstrate significantly stronger effects on NSCLC cells in response to combination therapy than to treatment with either agent alone,indicating that the combination of CET and STA9090 has potential synergistic effects.Additionally,the combination therapy inhibits tumor growth in a xenograft nude mouse model more effectively than treatment with either agent alone,suggesting improved efficacy when used together.Furthermore,the synergistic effects of the combination therapy are likely due to inactivation of the receptor tyrosine kinase(RTK)pathway,which is overly activated in cancer and contributes to tumor growth,angiogenesis,and metastasis.Consequently,our findings suggest that STA9090 has potent direct antitumor activity and synergizes with CET against NSCLC tumors.It is highly likely that these synergistic effects are mediated through RTK pathway inactivation caused by the combination.Therefore,our findings strongly and consistently support the potential synergistic effect of STA9090,an RTK inhibitor,in combination with EGFR-targeting agents.

关 键 词：CETUXIMAB STA9090 synergistic effect receptor tyrosine kinase non-small cell lung cancer 

分 类 号：R73[医药卫生—肿瘤]