Its prognosis has not improved significantly since the introduction of the chemotherapy regimen established about 40 years ago, highlighting the need for new therapeutic strategies.<h4>Aims</h4>The present study was undertaken to assess the effectiveness of combined inhibition of two promising drug targets, ATR and ribonucleotide reductase (RNR), in osteosarcoma cells.<h4>Methods and results</h4>The ATR inhibitor berzosertib and the RNR inhibitors triapine and didox were tested in TP53 wild-type (U2OS, MG-63) and mutant (SaOS-2) osteosarcoma cell lines. Here, TP53 is linked to osteosarcoma.