Despite the intensification of chemotherapy regimen, 5 years survival rates for patients with metastatic or relapsed osteosarcoma (OS) remains of 20%. The secreted factor netrin 1 (Nt1) is overexpressed in many human cancers to block apoptosis. Recent studies showed that blocking Nt1 interaction with its receptors potentiates chemotherapy efficacy suggesting that combining chemotherapies with Nt1 interference could be a promising approach for chemoresistant tumors like OS.
Analyses of the ATGSarc database (http://atg-sarc.sarcomabcb.org/), indicate that Sarcoma with complex genomic (SCG) with a higher expression of Nt1 have a poorer outcome (p
As pre operative treatment, Dox/aNt1 combination caused a marked delay in OS progression (median end point reached at day 17 and day 22 respectively in Dox and Dox/aNt1 group, (p 5mm) were found respectively in 75% and 17% of Dox and Dox/aNt1 treated rats As post operative treatment, Dox/aNt1combination significantly increased animals survival (median end point reached at day 15 and day 21 respectively in Dox and in Dox/aNt1 group; (p
Our study reporting the antiproliferative and antimetastatic effects and of Dox/aNt1 Combination in OS indicate that this combined treatment could be a way to overcome OS chemoresistance.
Clinical trial identification
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All authors have declared no conflicts of interest.