Emerging next-generation sequencing-based discoveries for targeted osteosarcoma therapy

Osteosarcoma (OS) is the most common primary bone malignancy and is frequently lethal via metastasis to the lung. While surgical techniques and adjuvant chemotherapies have emerged to combat this deadly cancer, the 5-year survival rate has plateaued over the past four decades. Therapeutic progress has been notably poor because past technologies have not been able to reveal obscured OS biomarkers and targets. With the advent and implementation of large-scale next-generation sequencing (NGS) studies, various somatic mutations and copy number changes involved in OS progression and metastasis have surfaced. These findings have significantly expanded the amount of genome-informed pathways and candidate genes suitable for targeting in pre-clinical models. Furthermore, NGS analyses comparing primary and matched pulmonary metastatic tumor tissues have catalogued previously unknown prognostic biomarkers in OS. In this review, we delineate the most recent findings in NGS for OS therapy and how this technology has advanced personalized therapy.