Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment

Hua Sun, Song Cao, R. Jay Mashl, Chia-Kuei Mo, Simone Zaccaria, Michael C. Wendl, Sherri R. Davies, Matthew H. Bailey, Tina M. Primeau, Jeremy Hoog, Jacqueline L. Mudd, Dennis A. Dean (+148 others)
2021 Nature Communications  
AbstractDevelopment of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic
more » ... driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs' recapitulation of human tumors.
doi:10.1038/s41467-021-25177-3 pmid:34429404 pmcid:PMC8384880 fatcat:t53uwnhuszbcfhsh734gh4yioy