Osteosarcoma and Ewing’s sarcoma, the two most frequent malignant primary
tumors preferentially arise in children and young adults, and have a poor prognosis. TRAIL
represents a promising therapeutic approach for most cancers but in the case of primary
bone tumors, osteosarcoma cell lines are highly resistant to this pro-apoptotic cytokine.
In addition, another signaling pathway mediating cell proliferation and migration may be
even activated in this subset of resistant cells leading to protumoral effect. Therapeutic
perspectives are linked to possibility to overcome TRAIL resistance by combining other
drugs with TRAIL or death receptors agonistic antibodies. We hypothesized that the bone
microenvironment may provide a favorable niche for TRAIL resistance that might be targeted
by new resensitizing agents