Targeting the EphA2 pathway: could it be the way for bone sarcomas?

Cell Commun Signal. 2024 Sep 9;22(1):433. doi: 10.1186/s12964-024-01811-7.

Abstract

Bone sarcomas are malignant tumors of mesenchymal origin. Complete surgical resection is the cornerstone of multidisciplinary treatment. However, advanced, unresectable forms remain incurable. A crucial step towards addressing this challenge involves comprehending the molecular mechanisms underpinning tumor progression and metastasis, laying the groundwork for innovative precision medicine-based interventions. We previously showed that tyrosine kinase receptor Ephrin Type-A Receptor 2 (EphA2) is overexpressed in bone sarcomas. EphA2 is a key oncofetal protein implicated in metastasis, self-renewal, and chemoresistance. Molecular, genetic, biochemical, and pharmacological approaches have been developed to target EphA2 and its signaling pathway aiming to interfere with its tumor-promoting effects or as a carrier for drug delivery. This review synthesizes the main functions of EphA2 and their relevance in bone sarcomas, providing strategies devised to leverage this receptor for diagnostic and therapeutic purposes, with a focus on its applicability in the three most common bone sarcoma histotypes: osteosarcoma, chondrosarcoma, and Ewing sarcoma.

Keywords: Bone sarcomas; Drug delivery; EphA2; Immunotherapy; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / metabolism
  • Bone Neoplasms* / pathology
  • Humans
  • Molecular Targeted Therapy
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Receptor, EphA2* / genetics
  • Receptor, EphA2* / metabolism
  • Sarcoma / genetics
  • Sarcoma / metabolism
  • Sarcoma / pathology
  • Signal Transduction*

Substances

  • Receptor, EphA2
  • EPHA2 protein, human