Strategies for targeting chondrosarcomas in vivo and molecular dissection of oncogenic events in chondrosarcomas: is epigenetics the culprit?

TL;DR

This paper reviews the molecular pathways involved in chondrosarcomas, emphasizing the interplay of epigenetic and non-epigenetic factors, and discusses potential combined therapeutic strategies targeting these pathways in vivo.

Contribution

It provides a comprehensive analysis of key oncogenic pathways in chondrosarcomas and proposes combined epigenetic and non-epigenetic targeted therapies.

Findings

Identification of key pathways like PI3K-AKT, EGFR, c-myc, and IDH1 mutations

Recurrent interactions between epigenetic and non-epigenetic actors

Strategies for in vivo targeting of chondrosarcomas

Abstract

It is obvious that both epigenetic and non-epigenetic actors contribute to tumorigenesis in chondrosarcomas and more generally in other cancers. Thus, the main altered pathways in chondrosarcomas are now well established and include both epigenetic and non-epigenetic pathways such as the PI3K-AKT signaling, EGFR overexpression, SPARC overexpression, c-myc overexpression, IHH/GLI1 axis, loss of Rb function, HIF1-alpha stabilization, IDH1 mutations, hypermethylation and SIRT1. This review aims to provide a detailed analysis of these pathways and highlights recurrent interactions between non-epigenetic and epigenetic actors in chondrosarcomas, raising the intriguing possibility of developing therapeutics targeting both epigenetic and non-epigenetic actors and supporting data from previous studies. Finally, we propose some strategies for targeting chondrosarcomas in vivo based on properties of this tumor.