Liquid biopsies in primary and secondary bone cancers

Abstract

Liquid biopsies are a powerful tool to non-invasively analyze tumor phenotype and progression as well as drug resistance. In the bone oncology field, liquid biopsies would be particularly important to develop, since standard biopsies can be very painful, dangerous (e.g., when found in proximity to the spinal cord), and hard to collect. In this review, we explore the recent advances in liquid biopsies in both primary (osteosarcoma and Ewing sarcoma) and secondary bone cancers (breast, prostate, and lung cancer-induced bone metastases), presenting their current role and highlighting their unexpressed potential, as well as the barriers limiting their possible adoption, including costs, scalability, reproducibility, and isolation methods. We discuss the use of circulating tumor cells, cell-free circulating tumor DNA, and extracellular vesicles for the purpose of improving diagnosis, prognosis, evaluation of therapy resistance, and driving therapy decisions in both primary and secondary bone malignancies.

Keywords: Ewing sarcoma; Liquid biopsy; bone metastasis; drug resistance; extracellular vesicles; minimal residual disease; osteosarcoma.

Figure 1

Liquid biopsies in primary and secondary bone cancers. Cell-free ctDNA, CTCs, and EVs are released into the general circulation by both primary (osteosarcoma and Ewing sarcoma) and secondary (breast, lung, and prostate) cancers and can be collected with a simple blood draw. Studying these three cancer-derived components by molecular or cellular analysis is termed liquid biopsy. Much information about the tumor can be achieved by analyzing CTCs, ctDNA, and EVs, making liquid biopsies a minimally invasive alternative to classical biopsies. Created with BioRender.com. ctDNA: Circulating tumor DNA; CTCs: circulating tumor cells; EVs: extracellular vesicles.