Xin-Shuai Wang1, Li Zhang1, Xiaocen Li2, De-Jiu Kong1, Xiao-Chen Hu1, Xue-Zhen Ding1, Jun-Qiang Yang1, Meng-Qi Zhao1, Yixuan He2, Kit S Lam2, She-Gan Gao1, Tzu-Yin Lin3, Yuanpei Li2. 1. Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan, University of Science & Technology, Luoyang 471003, China. 2. Department of Biochemistry & Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA. 3. Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA.
Abstract
AIM: This study aims to develop new nanoformulations of EGFR T790M targeted inhibitor AZD9291 and paclitaxel (PTX) for combination therapy of lung cancer. MATERIALS & METHODS: We prepared and characterized PTX- and AZD9291-loaded disulfide cross-linking micelles (DCMs), and evaluate their combination effect and toxicity in vitro and in lung cancer-bearing mice. RESULTS: Drug-loaded DCMs were relatively small in size, and possessed glutathione-responsive drug release. The combination of PTX-DCMs and AZD92921-DCMs exhibited strong synergistic effects in both cell line and in vivo without additional toxicity. Molecular studies demonstrated the synergistic modification in both IKB-α/NF-κB/Bcl-2 and EGFR/Akt pathways. CONCLUSION: The combination of DCM-loaded AZD9291 and PTX could potentially offer more effective and less toxicity treatment options for lung cancer patients.
AIM: This study aims to develop new nanoformulations of EGFR T790M targeted inhibitor AZD9291 and paclitaxel (PTX) for combination therapy of lung cancer. MATERIALS & METHODS: We prepared and characterized PTX- and AZD9291-loaded disulfide cross-linking micelles (DCMs), and evaluate their combination effect and toxicity in vitro and in lung cancer-bearing mice. RESULTS: Drug-loaded DCMs were relatively small in size, and possessed glutathione-responsive drug release. The combination of PTX-DCMs and AZD92921-DCMs exhibited strong synergistic effects in both cell line and in vivo without additional toxicity. Molecular studies demonstrated the synergistic modification in both IKB-α/NF-κB/Bcl-2 and EGFR/Akt pathways. CONCLUSION: The combination of DCM-loaded AZD9291 and PTX could potentially offer more effective and less toxicity treatment options for lung cancer patients.
Authors: Roy S Herbst; Diane Prager; Robert Hermann; Lou Fehrenbacher; Bruce E Johnson; Alan Sandler; Mark G Kris; Hai T Tran; Pam Klein; Xin Li; David Ramies; David H Johnson; Vincent A Miller Journal: J Clin Oncol Date: 2005-07-25 Impact factor: 44.544