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. 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.