# HMGB1 and Its Signaling Pathway in Osteosarcoma: Current Advances in Targeted Therapy

## TL;DR

This paper reviews how HMGB1 and its signaling pathways contribute to osteosarcoma and their potential for targeted therapy.

## Contribution

The paper summarizes recent findings on HMGB1's role in osteosarcoma and suggests future directions for multi-channel interventions.

## Key findings

- HMGB1 promotes osteosarcoma cell proliferation and immune escape via RAGE, TLR4, and downstream pathways.
- Interfering with HMGB1 shows antitumor potential in preclinical models but faces challenges in clinical translation.
- Future strategies include multi-channel interventions and efficient delivery systems to improve treatment outcomes.

## Abstract

This article reviews the research progress for high-mobility group protein B1 (HMGB1) and its signaling pathway in osteosarcoma (OS) and discusses its application potential in targeted therapy. A large number of domestic and foreign studies were reviewed to summarize the research results on the the biological function, signal pathway regulation mechanism, and intervention strategy of HMGB1 in recent years. HMGB1 promotes OS cell proliferation, invasion, and immune escape by activating RAGE, TLR4, and downstream MAPK, NF-κB, and PI3K/AKT signaling pathways. Interfering with HMGB1 or its signaling axis shows good antitumor potential in in vitro and in vivo models, but clinical transformation is still limited by its dual biological effects and tumor heterogeneity. HMGB1 and its related signaling pathways are important targets for the treatment of osteosarcoma. In the future, the development of a multi-channel combined intervention and efficient delivery system will provide a new direction for improving the therapeutic effect.