肾癌信号通路及免疫治疗进展课件

肾癌信号通路及免疫治疗进展肾癌信号通路及免疫治疗进展1肾癌信号通路及免疫治疗进展课件2调控肿瘤血管生成的信号通路VHL-HIF-VEGFPI3K-Akt-mTOR调控肿瘤血管生成的信号通路VHL-HIF-VEGF3VHL-HIF-VEGFCampbell-Walsh Urology 10th edVHL-HIF-VEGFCampbell-Walsh Uro4Santoni M et al.Int J Cancer.(2014)Santoni M et al.Int J Cancer.5Buczek M et al.Biochim Biophys Acta.(2014)Buczek M et al.Biochim Biophy6PI3K-Akt-mTORAlbiges L et al.Oncologist.(2012)PI3K-Akt-mTORAlbiges L et al.7Dienstmann R et al.Mol Cancer Ther.(2014)Dienstmann R et al.Mol Cancer8How can we manage resistanceAdjusting dosecombination therapySwitch to another targeted therapyDevelopment of novel agents targetingHouk BE et al.Cancer Chemother Pharmacol.(2010)How can we manage resistanceAd9肾癌的免疫治疗IFNIL-2VaccineSantoni M et al.Int J Cancer.(2014)肾癌的免疫治疗IFNSantoni M et al.Int10Checkpoint inhibitorKyi C,et al.FEBS Lett.(2014)Checkpoint inhibitorKyi C,et 11CTLA4PD-1T细胞表达时间抗原接触后48h抗原长期接触后产生配体表达由抗原提呈细胞表达CD80(B7.1)/CD80(B7.2)肿瘤或炎性组织表达PD-L1(B7-H1)抗原提成细胞表达PD-L2(B7-DC)小鼠相关基因敲除由于自身免疫反应导致迅速死亡由于自身免疫反应导致慢性死亡阻断后反应抗肿瘤T细胞特异性弱抗肿瘤T细胞特异性强CTLA-4与PD-1区别CTLA4PD-1T细胞表达时间抗原接触后48h抗原长期接触PD-1/PD-L1 blockade in RCCPD-1/PD-L1 blockade in RCC13PD-1Thompson RH,et al.Clin Cancer Res.(2007)PD-1Thompson RH,et al.Clin C14Thompson RH,et al.Clin Cancer Res.(2007)Thompson RH,et al.Clin Cance15PD-L1Thompson RH,et al.Cancer Res.(2006)PD-L1Thompson RH,et al.Cance16Jilaveanu LB et al.J Cancer.(2014)Jilaveanu LB et al.J Cancer.17肾癌信号通路及免疫治疗进展课件18肾癌信号通路及免疫治疗进展课件19肾癌信号通路及免疫治疗进展课件20primary end point:comparison of PFS to assess whether a dose-response relationship exists.Secondary end points:PFS,objective response rate(ORR),time to response,duration of response,overall survival(OS),and AE rate.primary end point:comparison21肾癌信号通路及免疫治疗进展课件22肾癌信号通路及免疫治疗进展课件23肾癌信号通路及免疫治疗进展课件24肾癌信号通路及免疫治疗进展课件25肾癌信号通路及免疫治疗进展课件26肾癌信号通路及免疫治疗进展课件27肾癌信号通路及免疫治疗进展课件28肾癌信号通路及免疫治疗进展课件29肾癌信号通路及免疫治疗进展课件30Tripathi A,et al.BioDrugs.(2014)Tripathi A,et al.BioDrugs.(31Philips GK,et al.Int Immunol.(2014)Philips GK,et al.Int Immunol32肾癌信号通路及免疫治疗进展课件33肾癌信号通路及免疫治疗进展课件34Cancer ImmunotherapyAscierto PA,et al.J Transl Med.(2014)Cancer ImmunotherapyAscierto P35谢谢 谢！谢！谢 谢！36