Preclinical Development – Chemical
2019 PharmSci 360
If a cancer can be mimicked by a cell line, how to find the proper one for research? The aim of this study is to develop a prioritize system for cancer cell line selection by integrated analysis of cancer cell lines and tumor samples.
By integrated data resource from CCLE and TCGA, a computational method is proposed to prioritize 779 cell lines by accounting the number of matched patients from TCGA. For each subtype of cancer, ranking scores RStop, the most similar score, and RSbottom, the most dissimilar score, were calculated based on gene expression pattern between cell line and patient.
Validation experiments on predicted top cell line with the closest resemblance to a certain tumor group were conducted using FDA-approved drugs on breast and thyroid carcinoma. The CCL-GPS on papillary bladder carcinoma was applied to screen the potential antitumor drugs among 1068 FDA-approved drug library for drug repurposing. Additionally, a web tool (http://tcm.zju.edu.cn/cclgps) has been developed to allow the on-the-fly evaluation, which offers good insight for drug screening or mechanism study.