Establishment Of Patient-derived Tumor Mouse Model Of Breast Cancer And Efficacy Of MLN4924 Combined With Radiotherapy

To improve tumor's take rate and shorten time of developing patient-derived breast tumor xenograft model,observe pathologic differences between patient breast cancer tissue and tumors at each generation in mice and evaluate the anti-tumor efficacy of MLN4924 as a NAE inhibitor combined with radiotherapy in PDTX breast cancer model in mice.Establishment of patient-derived human breast cancer xenografts model by estrodiol implantation and four sides' method,collect tumors of each generation for pathologic examination and evaluate anti-tumor efficacy of MLN4924 as a NAE inhibitor combined with radiotherapy in subcutaneous breast model of BR-05-0028 in female BALB/c nude mice.In this study,the tumor take rate is 12% and tumor formation rate in different generations is 100%.Two models are belong to estrogen-dependents and the other two are estrogen-independent.Compared with the tumor growth curve for estrogen-independent's model in different generations,the speed of tumor with estrodiol is quicker than without it.Implantation with four sides' method can shorten time of developing patient-derived breast tumor xenograft model.The tumor tissues from P1 to P3 were similar to clinical specimens by pathologic examination.Compared to vehicle group,MLN4924 as a single treatment produced no significant anti-tumor activities.But when combined with radiotherapy produced significant anti-tumor activities comparing to vehicle,MLN4924 and radiotherapy.This study has successfully improved tumor take rate and shortened time of developing patient-derived breast tumor xenograft model.The tumor tissues from P1 to P3 are similar to clinical specimens and accurately evaluated the anti-tumor efficacy of MLN4924 as a NAE inhibitor combined with X-ray radiotherapy in PDTX breast cancer model BR-05-0028 in BALB/c nude mice.