Osteosarcoma Treatment and Prognosis

Osteosarcoma is the most common primary malignant bone tumour, predominantly affecting adolescents and young adults. Standard management combines wide surgical resection with multiagent chemotherapy, most often a methotrexate–doxorubicin–cisplatin (MAP) regimen administered both before (neoadjuvant) and after (adjuvant) surgery. This approach has raised five-year survival rates for localised disease to around 60–70%, yet outcomes have plateaued over recent decades. Prognosis is markedly poorer in patients presenting with pulmonary or non-pulmonary metastases, axial-skeleton involvement or a suboptimal histological response to preoperative chemotherapy. Advances in molecular profiling have revealed extensive genetic and epigenetic heterogeneity, underscoring challenges to targeted therapy. At the same time, an evolving understanding of the tumour microenvironment and immune landscape has opened new avenues for intervention, including immunomodulatory agents and small-molecule inhibitors. Current efforts seek to personalise treatment by integrating prognostic biomarkers, novel drug targets and adaptive trial designs to improve outcomes in high-risk and relapsed cases.

Research from Nature Portfolio

Systematic mapping of RNA–protein interactions in osteosarcoma cells has uncovered widespread alterations in RNA-binding protein (RBP) activities compared with normal osteoblasts. Integrated proteomic and transcriptomic analyses identified several RBPs whose dysregulated binding drives translation of oncogenic programmes. Notably, a feedback axis between the RBP IGF2BP3 and the transcription factor Myc emerges as a key vulnerability: inhibition of translation selectively impairs tumour cell viability. These findings point to translation machinery components as potential therapeutic targets.

A comprehensive single-cell RNA atlas of primary, recurrent and metastatic osteosarcoma lesions has delineated eleven distinct cellular states, including malignant osteoblastic and chondroblastic subpopulations, stromal fibroblasts and immune infiltrates. Intratumoural heterogeneity was highlighted by transdifferentiation trajectories and variable immune cell compositions. Crucially, blockade of the immune checkpoint TIGIT enhanced cytotoxic T-cell activity against osteosarcoma cells ex vivo, illustrating proof of concept for immune-based therapies tailored to the tumour’s cellular ecosystem.

Osteosarcoma Treatment and Prognosis publication trend

The graph below shows the total number of articles in osteosarcoma treatment and prognosis across all publications each year (not limited to Nature Index journals).

Technical terms

Neoadjuvant chemotherapy: Drug treatment given before surgical resection to shrink the tumour and assess histological response.

Histological response: Degree of tumour cell death observed microscopically after neoadjuvant therapy, often expressed as percentage of necrosis.

Event-free survival (EFS): Time from diagnosis or start of treatment until occurrence of relapse, progression, secondary malignancy or death.

Tumour microenvironment: The complex milieu of non-malignant cells, extracellular matrix and signalling molecules surrounding and interacting with cancer cells.

Immune checkpoint blockade: Therapeutic inhibition of regulatory pathways (e.g. PD-1, TIGIT) that restrain T-cell activity, to enhance anti-tumour immunity.

References

1. Systematic analysis of RNA-binding proteins identifies targetable therapeutic vulnerabilities in osteosarcoma. Nature Communications (2024).
2. Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma. Nature Communications (2020).
3. Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. European Journal of Cancer (2019).
4. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. The Lancet Oncology (2016).
5. The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem. Cells (2020).