Precision Medicine in Osteosarcoma: MATCH Trial and Beyond

Abstract

Osteosarcoma (OS) is a rare bone malignant tumour with a poor prognosis in the case of recurrence. So far, there is no agreement on the best systemic therapy for relapsed OS. The availability of next generation sequencing techniques has recently revolutionized clinical research. The sequencing of the tumour and its matched normal counterpart has the potential to reveal a wide landscape of genetic alterations with significant implications for clinical practice. The knowledge that the genomic profile of a patient’s tumour can be precisely mapped and matched to a targeted therapy in real time has improved the development of precision medicine trials (PMTs). PMTs aiming at determining the effectiveness of targeted therapies could be advantageous for patients with a tumour refractory to standard therapies. Development of PMTs for relapsed OS is largely encouraging and is in its initial phase. Assessing OS features, such as its rarity, its age distribution, the technical issues related to the bone tissue origin, and its complex genomic landscape, represents a real challenge for PMTs development. In this light, a multidisciplinary approach is required to fully exploit the potential of precision medicine for OS patients.

RAMP1 as a Novel Prognostic Biomarker in Pan-cancer and Osteosarcoma

“…Additionally, considering the crucial role of immune cell in ltration in the tumor-immune microenvironment during the progression of OS 27 , we further explored the association between the intratumoral immune microenvironment and RAMP1 in OS. Notably, we observed signi cant differences in the in ltration of two immune cell types, speci cally T cells CD4 memory activated and T cells gamma delta (γδ T Cells), between patients with OS who had high and low RAMP1 expression.…”

RAMP1 as a novel prognostic biomarker in pan-cancer and osteosarcoma

“…Additionally, considering the crucial role of immune cell infiltration in the tumor-immune microenvironment during the progression of OS [ 28 ], we further explored the association between the intra-tumoral immune microenvironment and RAMP1 in OS. Notably, we observed significant differences in the infiltration of two immune cell types, specifically T cells CD4 memory activated and T cells gamma delta (γδ T Cells), between patients with OS who had high and low RAMP1 expression.…”

Advances in Target Therapy Research in Osteosarcoma

“…This information can be used to identify specific therapeutic targets within tumor cells, enabling the targeted use of drugs or therapies that may be most effective against those specific mutations or markers, to allow the choice of treatments best suited to the molecular profile of a patient's tumor, avoiding treatments that may not be effective or potentially harmful and to use molecular testing to monitor the tumor's response to treatment over time and make any therapeutic changes or adjustments based on the patient's response. So, precision medicine, thanks to developments in genomics and the understanding of the molecular mechanisms of tumors, is helping to improve therapeutic options and the management of patients with osteosarcoma [34]. The increasing use of Next Generation Sequencing (NGS) has completely revolutionized clinical research over the last decade [35]; particularly, exome sequencing can be used to better understand the genetic causes underlying the development of osteosarcoma [36] thanks to the integration of molecular and clinical data to obtain a more complete and accurate view of the disease and develop personalized therapeutic approaches.…”