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

Zhuosheng Liu1, Fucai Wang1, Zhihan Zhou1

  • 1School of Medicine, Huaqiao University, Quanzhou 362021, China.

Current Issues in Molecular Biology
|November 26, 2025
PubMed

Insights

High-mobility group protein B1 (HMGB1) fuels osteosarcoma growth and immune evasion. Targeting HMGB1 and its pathways shows promise for osteosarcoma treatment, though clinical use faces challenges.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • High-mobility group protein B1 (HMGB1) is implicated in various cancers.
  • Its role in osteosarcoma (OS) pathogenesis and therapeutic potential requires comprehensive review.

Purpose of the Study:

  • To review current research on HMGB1 and its signaling pathways in osteosarcoma.
  • To discuss the therapeutic application potential of targeting HMGB1 in OS.

Main Methods:

  • Systematic review of domestic and international studies on HMGB1 in osteosarcoma.
  • Analysis of HMGB1's biological functions, signaling pathways, and intervention strategies.

Main Results:

  • HMGB1 promotes OS cell proliferation, invasion, and immune escape via RAGE, TLR4, MAPK, NF-κB, and PI3K/AKT pathways.
  • Interference with HMGB1 or its signaling axis demonstrates antitumor potential in preclinical models.
  • Clinical translation is hindered by HMGB1's dual effects and OS tumor heterogeneity.

Conclusions:

  • HMGB1 and its signaling pathways represent crucial therapeutic targets for osteosarcoma.
  • Future strategies may involve multi-channel interventions and advanced delivery systems for improved efficacy.
Keywords:
high-mobility group box 1osteosarcomasignaling pathwaytargeted therapy

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