# From Bench to Bedside: Advancements in Precision Oncology and Drug Discovery for Osteosarcoma

## TL;DR

This paper reviews new approaches in osteosarcoma treatment, focusing on precision medicine, immunotherapy, and nanotechnology to improve outcomes for patients.

## Contribution

The paper highlights novel therapeutic strategies like immunotherapy, nanotechnology, and multi-omics approaches for osteosarcoma.

## Key findings

- Conventional therapies for osteosarcoma have significant limitations, including toxicity and drug resistance.
- Emerging strategies like immunotherapy, nanotechnology, and CRISPR-Cas9 show promise in improving treatment outcomes.
- Multi-omics and digital pathology are advancing personalized treatment approaches for osteosarcoma.

## Abstract

Osteosarcoma is the most frequent bone tumour in children and young adults. The current strategy for osteosarcoma therapy includes high doses of methotrexate (HD-MTX), doxorubicin, and cisplatin combined with surgery. Established in 1970s, this approach presents several limitations, particularly in metastatic and recurrent cases. This review aims to investigate and highlight emerging discoveries to improve osteosarcoma care. We intend to focus on immunotherapy and target therapy, as well as on nanotechnology-based therapeutic strategies, highlighting the improvements on delivery and distribution of therapy. Moreover, we will shed light on multi-omics approaches which could help in the discovery of new prognostic markers or genetic targets for precision medicine.

Osteosarcoma remains a highly aggressive malignancy with limited therapeutic progress and poor outcomes, particularly in metastatic or recurrent cases. Conventional treatment approaches, primarily based on surgery and high-dose chemotherapy, are hindered by significant drawbacks, including severe toxicity, high relapse rates, and drug resistance, underscoring the inadequacy of current standard approaches. This review examines emerging advances in precision medicine and drug discovery, including targeted inhibitors, immunomodulatory agents, combination treatments, and advanced biomaterials, that promise to transform osteosarcoma care. Recent advances, such as combinations of immune checkpoint inhibitors with novel agents or nanoparticle-based drug delivery systems, as well as CRISPR-Cas9 gene-editing applications, offer new strategies to overcome the inherent challenges of conventional therapies. In addition, cutting-edge research leveraging multi-omics analyses and digital pathology is refining our understanding of the tumour microenvironment, paving the way for more individualised treatment strategies.