Paclitaxel resistance in isogenic PDX

Tumor heterogeneity and resistance to chemotherapy represents a significant challenge in the clinical management of triple negative breast cancer (TNBC). By dissecting molecular pathways associated with treatment resistance, we sought to define patient sub-groups and define actionable targets for next-line treatment. Bulk RNA sequencing were performed on isogenic patient-derived xenografts (PDX) representing paclitaxel-sensitive and -resistant tumors. Pathways identified as upregulated in the resistant model were further explored as targets in downstream approcaches, and their clinical relevance evaluated in publicly available clincial data. Overall design: Resistance to paclitaxel were generated in mice by continous treatment of triple negative breast cancer patient-derived xenograft. The isogenic pair of the parental MAS98.12 and resistance derived MAS98.12PR were subjected to RNAseq.