TARGETING ANGIOGENESIS IN OSTEOSARCOMA: ADDITION OF REPURPOSED HEMOSTATIC DRUG DESMOPRESSIN TO BEVACIZUMAB AS A THERAPEUTIC STRATEGY

SOLERNÓ LM; SAUD ZY; LLAVONA C; GONZÁLEZ MORÁN F; GOTTARDO MF; ANDERSEN M; CARDAMA GA; ALONSO DF; GARONA J

Mar del Plata

Congreso; REUNION ANUAL DE SOCIEDADES DE BIOCIENCIA; 2023

Sociedad Argentina de Investigación Clínica

Angiogenesis plays a crucial role in osteosarcoma (OSA) progres-sion, the most common primary malignant bone tumor. In thesehighly metastatic and vascularized tumors overexpression of VEGFcorrelates with poorer outcomes. Although promising, adding an-ti-VEGF bevacizumab to chemotherapy didn’t provide significantclinical benefits in OSA. Desmopressin (dDAVP) is a repurposedhemostatic drug in oncology that acts as a selective agonist forthe AVPR2 receptor present in blood microvessels and some can-cer cells. dDAVP has shown potent angiostatic and antimetastat-ic activity in other aggressive tumors but its antiangiogenic effectin OSA has never been studied. The objective of this work was toevaluate dDAVP effects on OSA-associated angiogenesis, alone orin combination with bevacizumab. After exploring interactive geneexpression web servers GEPIA2 and TIMER2.0 (SARC-TCGA/n=257), AVPR2 showed a positive prognostic impact on overall anddisease-free survival in sarcoma patients, and negatively correlatedwith proangiogenic genes (VEGFA, MEK, MTOR), as well as protu-moral immune infiltrates (MDSCs and M0 macrophages). Its expres-sion also correlated with different antitumoral immune cells such asNK cells, M1 macrophages, mast cells and CD4+ T cells. Moreover,AVPR2 was detected in human MG-63 OSA cells by qPCR and IHC.In an in vivo modified matrigel plug assay, dDAVP treatment (12 μg/kg i.v., 3 doses/week) notably reduced early angiogenic response inMG-63 incipient lesions. In nude mice bearing growing MG-63 xeno-grafts treatment with dDAVP (12 μg/kg i.v., 3 doses/week) in combi-nation with bevacizumab (5 mg/kg i.p., 2 doses/week) significantlyinhibited tumor progression, enhancing the anti-OSA effects of bothmonotherapies. Results were significant at p