Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target?

J Pathol Clin Res. 2021 Mar;7(2):165-172. doi: 10.1002/cjp2.191. Epub 2020 Dec 8.

Abstract

Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. More than a third of patients do not respond to standard therapy and urgently require alternative treatment options. Due to a high degree of inter- and intra-tumoural genomic heterogeneity and complexity, recurrent molecular alterations that could serve as prognostic predictors or therapeutic targets are still lacking in osteosarcoma. Copy number (CN) gains involving the IGF1R gene, however, have been suggested as a potential surrogate marker for treating a subset of patients with IGF1R inhibitors. In this study, we screened a large set of osteosarcomas and found specific CN gains of the IGF1R gene in 18 of 253 (7.1%) cases with corresponding IGF1R overexpression. Despite the discouraging results observed in clinical trials in other tumours so far, focusing only on selected patients with osteosarcoma that show evidence of IGF pathway activation might represent a promising new and innovative treatment approach.

Keywords: IGF1R; chromoanagenesis; osteosarcoma; targeted treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / pathology*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteosarcoma / drug therapy
  • Osteosarcoma / pathology*
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Signal Transduction*
  • Young Adult

Substances

  • IGF1R protein, human
  • Receptor, IGF Type 1