A Comparative Oncology Drug Discovery Pipeline to Identify and Validate New Treatments for Osteosarcoma.

Journal Article (Journal Article)

BACKGROUND: Osteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new treatments has been hampered by extensive genomic heterogeneity and limited access to patient samples to study the biology of this complex disease. METHODS: To overcome these barriers, we combined the power of comparative oncology with patient-derived models of cancer and high-throughput chemical screens in a cross-species drug discovery pipeline. RESULTS: Coupling in vitro high-throughput drug screens on low-passage and established cell lines with in vivo validation in patient-derived xenografts we identify the proteasome and CRM1 nuclear export pathways as therapeutic sensitivities in osteosarcoma, with dual inhibition of these pathways inducing synergistic cytotoxicity. CONCLUSIONS: These collective efforts provide an experimental framework and set of new tools for osteosarcoma and other rare cancers to identify and study new therapeutic vulnerabilities.

Full Text

Duke Authors

Cited Authors

  • Somarelli, JA; Rupprecht, G; Altunel, E; Flamant, EM; Rao, S; Sivaraj, D; Lazarides, AL; Hoskinson, SM; Sheth, MU; Cheng, S; Kim, SY; Ware, KE; Agarwal, A; Cullen, MM; Selmic, LE; Everitt, JI; McCall, SJ; Eward, C; Eward, WC; Hsu, DS

Published Date

  • November 11, 2020

Published In

Volume / Issue

  • 12 / 11

PubMed ID

  • 33187254

Pubmed Central ID

  • PMC7696249

International Standard Serial Number (ISSN)

  • 2072-6694

Digital Object Identifier (DOI)

  • 10.3390/cancers12113335


  • eng

Conference Location

  • Switzerland