EGFR is required for FOS-dependent bone tumor development via RSK2/CREB signaling

Area of Science:

• Oncology
• Molecular Biology
• Biomarker Discovery

Background:

• Osteosarcoma (OS) is a rare bone cancer with limited treatment options and stagnant survival rates.
• Epidermal growth factor receptor (EGFR) is highly expressed in OS, but its clinical significance remains unclear.
• Novel biomarkers and therapeutic strategies are urgently needed for osteosarcoma.

Purpose of the Study:

• To investigate the role of EGFR in osteosarcoma development and progression.
• To identify potential biomarkers for predicting response to anti-EGFR therapies in OS.
• To evaluate the therapeutic efficacy of anti-EGFR treatments in preclinical OS models.

Main Methods:

• Utilized an autochthonous c-Fos-dependent OS mouse model (H2-c-fosLTR) and human OS tumor biopsies.
• Investigated the effects of EGFR deletion/inhibition on tumor formation and cancer-initiating cell proliferation.
• Analyzed the correlation between EGFR and c-Fos expression and patient survival.
• Assessed the response of human OS xenografts to anti-EGFR therapy based on biomarker expression.

Main Results:

• EGFR deletion/inhibition reduced tumor formation in mice by inhibiting osteoblastic cancer-initiating cell proliferation via RSK2/CREB-dependent c-Fos expression.
• Co-expression of EGFR and c-Fos in OS patients was associated with reduced overall survival.
• Preclinical studies showed that only human OS xenografts expressing both EGFR and c-Fos responded to anti-EGFR therapy.

Conclusions:

• c-Fos plays a crucial role in EGFR-mediated osteosarcoma development.
• EGFR and c-Fos co-expression is a negative prognostic factor in osteosarcoma patients.
• c-Fos is a potential predictive biomarker for anti-EGFR therapy response in osteosarcoma.