In vivo expansion and propagation of malignant progenitor lineages for target discovery

In embryonic malignancies there exist "blastemal" progenitor lineages that propagate the tumors. Upon in vitro culture and expansion progenitor lineages are eliminated and tumor cells lose their tumor initiating capacities (TIC) in transplantation assays.

We have established patient derived xenografts (PDXs) from pediatric solid tumors which allow for propagation and expansion of the progenitor pool leading to enhancement of the tumor-initiating capacity in limiting dilution xenotransplantation assays. Sequential transcriptomics of propagatable PDXs along the increasing TIC axis and functional analysis led to identification of novel therapeutic targets in malignancies such as Wilms tumor, Malignant rhabdoid tumor, Pulmonary blastoma and Ewing sarcoma.