# Research status and prospects of molecular pathological mechanisms and novel therapeutic targets of osteosarcoma: a systematic review

## TL;DR

This review explores the molecular mechanisms and new treatment targets for osteosarcoma, a deadly bone cancer, and highlights future directions for precision therapy.

## Contribution

The paper systematically integrates multi-omics and clinical data to identify synergistic mechanisms and novel therapeutic strategies for osteosarcoma.

## Key findings

- Targeted therapies and immunotherapies show promise in improving osteosarcoma prognosis and response rates.
- Advanced technologies like nanotechnology and 3D-printed scaffolds offer new treatment and diagnostic capabilities.
- Challenges include tumor heterogeneity, off-target toxicity, and translational gaps in treatment efficacy.

## Abstract

The treatment of osteosarcoma, a highly aggressive primary malignant bone tumour, has long faced limitations due to chemotherapy resistance, tumour het-erogeneity, and an immunosuppressive microenvironment.

This review synthesizes recent multi-omics and clinical trial data to analyse synergistic oncogenic mechanisms in osteosarcoma—including driver mutations (TP53/RB1), epigenetic re-programming (m6A/ncRNA networks), and dysregulated pathways (PI3K/AKT, Wnt/β-catenin)—and evaluates derived therapeutic strategies.

Targeted therapies demonstrate potential to improve prognosis in clinical trials; immunotherapies significantly enhance response rates by remodelling the cold tumour microenvironment; advanced technologies like nanotechnology and 3D-printed scaffolds over-come limitations of conventional treatments and enable integrated diagnosis and therapy. However, tumour evolutionary heterogeneity, off-target toxicity of targeted therapies, and translational gaps between animal models and clinical efficacy remain major challenges.

Future directions require integrating AI-driven imaging omics, spatiotemporal multi-omics, and mechanically adaptive biomaterials to establish a precision management system. This will advance osteosarcoma therapy from survival prolongation toward functional cure—defined as complete tumour eradication with physiological reconstruction of bone structure/function (e.g., restoring load-bearing/joint mobility), while preventing treatment-related disability, ultimately achieving oncologic cure with preserved quality of life.