combination treatment with mek and akt inhibitors is more effective than each drug alone in human non-small cell lung cancer in vitro and in vivomek和akt抑制剂联合治疗更有效比每种药物单独使用人类非小细胞肺癌在体外和体内.pdf

Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non- Small Cell Lung Cancer In Vitro and In Vivo 1 1 1 2 3 3 Jieru Meng *, Bingbing Dai , Bingliang Fang , B. Nebiyou Bekele , William G. Bornmann , Duoli Sun , 3 4 4 5 5 Zhenghong Peng , Roy S. Herbst , Vassiliki Papadimitrakopoulou , John D. Minna , Michael Peyton , Jack A. Roth1 1 Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 2 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 3 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 4 Department of Thoracic/Head Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 5 Hamon Center for Therapeutic Oncology Research, and Simmons Cancer Center, The University of Texas Southwestern Medical Center at Dallas, Texas, United States of America Abstract AZD6244 and MK2206 are targeted small-molecule drugs that inhibit MEK and AKT respectively. The efficacy of this combination in lung cancer is unknown. Our previous work showed the importance of activated AKT in mediating resistance of non-small cell lung cancer (NSCLC) to AZD6244. Thus we hypothesized that dual inhibition of both downstream MEK and AKT pathways would induce synergis