Genomic complexity of osteosarcoma and its implication for preclinical and clinical targeted therapies

Courtney Schott, Avanthi Tayi Shah, E. Alejandro Sweet-Cordero

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Osteosarcoma is a genomically complex disease characterized by few recurrent single-nucleotide mutations or in-frame fusions. In contrast, structural alterations, including copy number changes, chromothripsis, kataegis, loss of heterozygosity (LOH), and other large-scale genomic alterations, are frequent and widespread across the osteosarcoma genome. These observed structural alterations lead to activation of oncogenes and loss of tumor suppressors which together contribute to oncogenesis. To date, few targeted therapies for osteosarcoma have been identified. It is likely that effectiveness of targeted therapies will vary greatly in subsets of tumors with distinct key driver events. Model systems which can recapitulate the genetic heterogeneity of this disease are needed to test this hypothesis. One possible approach is to use patient-derived xenograft (PDX) models characterized with regards to their similarity to the human tumor samples from which they were derived. Here we review evidence pointing to the genomic complexity of osteosarcoma and how this is reflected in available model systems. We also review the current state of preclinical testing for targeted therapies using these models.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer
Pages1-19
Number of pages19
DOIs
StatePublished - 2020
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1258
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • AKT
  • CCNE1
  • CDK4
  • Combination therapy
  • MYC
  • Patient-derived xenografts
  • PTEN
  • Targeted therapy
  • VEGFR

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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