Objective:

To evaluate the therapeutic potential of desmopressin (dDAVP) as a coadjuvant strategy to enhance the efficacy of Bevacizumab (BEVA) in treating osteosarcoma (OSA).

Approach:

• Bioinformatic Analysis: Analyzed AVPR2 expression and its associations with tumor aggressiveness, immune and stromal infiltration markers, and clinical outcomes using TCGA-SARC and TARGET-OS datasets.
• In Vitro Assessment: Assessed endothelial proliferation, migration, and morphogenesis in HmVEC-L and HMEC-1 microvascular cells.
• In Vivo Evaluation: Evaluated antitumor activity in human (MG-63) and murine (K7M3) OSA models, including xenogeneic and syngeneic models of tumor growth, metastasis, and angiogenesis.
• Combined Treatment Analysis: Investigated the effects of combined dDAVP and BEVA therapy in vitro and in vivo, focusing on histopathological endpoints.

Key Findings:

• AVPR2 expression was inversely associated with proangiogenic, prosurvival, and prometastatic gene signatures.
• Elevated AVPR2 expression correlated with improved survival in both pan-sarcoma and pediatric OSA cohorts.
• dDAVP significantly reduced pulmonary metastasis and vascularization in vivo.
• dDAVP enhanced the antivascular activity of BEVA under tumor-conditioned conditions.
• Combined treatment with dDAVP and BEVA significantly inhibited OSA xenograft progression without overt toxicity.

Interpretation:

The findings support further evaluation of dDAVP as a potential adjuvant therapy in OSA, particularly in combination with BEVA, targeting complementary angiogenesis-related mechanisms.

Limitations:

• The role of dDAVP in OSA-associated angiogenesis remains incompletely characterized.
• Further translational studies are needed to validate the findings.

Conclusion:

The study suggests that combining dDAVP with BEVA may improve therapeutic efficacy in osteosarcoma.