Mouse-Dog-Human Preclinical Cancer Model for Osteosarcoma Proposed

Drug screens in both canine and human osteosarcoma patient-derived xenograft mouse model and cell lines can identify targeted agents in osteosarcoma — and according to study results from researchers in veterinary medicine, the cancer-killing ability across a screen of 119 cancer drugs in both dog and human cell lines “demonstrated that canine and human osteosarcoma cell lines are indistinguishable.” These findings were presented at the Connective Tissue Oncology Society (CTOS) 2018 Annual Meeting in Rome, Italy.¹

The investigators sought to validate their so-called mouse-dog-human (MDH) personalized medicine pipeline in response to the high prevalence of osteosarcoma in dogs. More than 50,000 new diagnoses of osteosarcoma per year occur in dogs, compared with only 1000 new cases per year in humans. Plus, they noted that similarities between the species have already been well established.

To test just how closely these species are linked, they created 5 human and 4 canine PDX cell lines in which the 119 US Food and Drug Administration-approved drugs were tested. They also performed an expanded drug screen using the National Institute of Health’s Bioactive 2100 compound assay. Based on the results of the screens, bortezomib, verdinexor, and alvespimycin were selected for validation in vivo.

The drugs that were used to kill canine and human cancer cell lines performed similarly across both species, and they determined that proteasome inhibitors were “top drug candidates for all osteosarcoma cell lines alongside standard of care therapies.” Following an expanded drug screen, they concluded that verdinexor inhibited tumor growth (P < .05) in both human and canine PDX mouse models compared with controls (ie, cells treated with DMSO). Bortezomib reduced tumor growth in canine PDX models but not human PDX models, although both cell lines were sensitive to the drug in vitro. Alvespimycin was not efficacious in cell lines of either species, “highlighting the need for in vivo validation following in vitro drug screens.”

The researchers ultimately concluded that “on a population level, this cross-species approach could make significant contributions to discovering novel standard-of-care therapies.”

Read more of Cancer Therapy Advisor‘s coverage of the CTOS 2018 meeting by visiting the conference page.

Reference

1. Rao S, Altune E, Glover W, et al. Shifting the paradigm in preclinical cancer modeling: a mouse-dog-human personalized medicine pipeline to identify novel therapeutics for osteosarcoma. Presented at: CTOS 2018 Annual Meeting; Rome, Italy: November 14-17. Poster 015.