Osteosarcoma through the Lens of Bone Development, Signaling, and Microenvironment

Elizabeth P Young; Amanda E Marinoff; Eunice Lopez-Fuentes; E Alejandro Sweet-Cordero

doi:10.1101/cshperspect.a041635

Osteosarcoma through the Lens of Bone Development, Signaling, and Microenvironment

Cold Spring Harb Perspect Med. 2024 Apr 2:a041635. doi: 10.1101/cshperspect.a041635. Online ahead of print.

Authors

Elizabeth P Young^#¹, Amanda E Marinoff^#¹, Eunice Lopez-Fuentes¹, E Alejandro Sweet-Cordero²

Affiliations

¹ Division of Pediatric Oncology, Department of Pediatrics, University of California San Francisco, San Francisco, California 94158, USA.
² Division of Pediatric Oncology, Department of Pediatrics, University of California San Francisco, San Francisco, California 94158, USA alejandro.sweet-Cordero@ucsf.edu.

^# Contributed equally.

PMID: 38565264
DOI: 10.1101/cshperspect.a041635

Abstract

In this work, we review the multifaceted connections between osteosarcoma (OS) biology and normal bone development. We summarize and critically analyze existing research, highlighting key areas that merit further exploration. The review addresses several topics in OS biology and their interplay with normal bone development processes, including OS cell of origin, genomics, tumor microenvironment, and metastasis. We examine the potential cellular origins of OS and how their roles in normal bone growth may contribute to OS pathogenesis. We survey the genomic landscape of OS, highlighting the developmental roles of genes frequently altered in OS. We then discuss the OS microenvironment, emphasizing the transformation of the bone niche in OS to facilitate tumor growth and metastasis. The role of stromal and immune cells is examined, including their impact on tumor progression and therapeutic response. We further provide insights into potential development-informed opportunities for novel therapeutic strategies.