Canine models for characterization, diagnosis, and treatment of human cancers using comparative canine-human transcriptomics

National Center For Advancing Translational Sciences

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Abstract

We previously identified 262 tissue-expressed proteins associated with particular cancers (lung adenocarcinoma, melanoma, osteosarcoma, B- and T-cell lymphoma), leading to identification of a set of 60 approved drugs known to affect the expression of said proteins. Single-compound cell-based screens identified 40 drugs with cancer cell-killing effects, while subsequent matrix screens identified a set of 20 two-drug combinations that exhibited synergy in cancer cell-killing experiments. This year, data from previous high-throughput drug combination matrix screenings were analyzed, leading to the identification of 17 additional synergistic two-drug combinations that demonstrated activity in both canine (TOT) and human (MG63.3) osteosarcoma cell lines. Several of these promising combinations have been selected for further evaluation in mouse patient-derived xenograft (PDX) models of osteosarcoma, with in vivo studies scheduled to commence in the coming year.