Osteosarcoma as a communication-driven disease: redefining tumor-bone signaling networks as therapeutic targets

Area of Science:

• Oncology
• Cancer Biology
• Tumor Microenvironment

Background:

• Osteosarcoma (OS) is an aggressive bone cancer with high metastatic potential.
• Genomic instability alone doesn't explain OS; intercellular communication is key.
• The tumor microenvironment significantly influences OS progression and treatment resistance.

Purpose of the Study:

• To review the role of intercellular communication in Osteosarcoma.
• To integrate knowledge on signaling networks within the OS tumor microenvironment.
• To identify novel therapeutic vulnerabilities by framing OS as a communication-driven ecosystem.

Main Methods:

• Literature review integrating current knowledge on OS signaling.
• Analysis of immune cell crosstalk, extracellular vesicles, soluble factors, and direct cell-cell interactions.
• Discussion of how communication circuits shape the tumor immune microenvironment and plasticity.

Main Results:

• Intercellular signaling networks critically regulate OS growth, immune evasion, metastasis, and therapy resistance.
• Communication circuits coordinate local and systemic tumor progression.
• These networks shape the tumor immune microenvironment and drive adaptive plasticity.

Conclusions:

• Osteosarcoma progression is heavily influenced by complex intercellular communication.
• Disrupting these pathological signaling networks presents emerging therapeutic strategies.
• Further clinical validation is needed for many communication-targeted approaches in OS.