SAR405838 activates the p53 pathway, increases the expression of PUMA and P21, and induces complete tumor regression in SJSA-1 osteosarcoma xenograft mice.354 The safety of SAR405838 alone355 or in combination with MEK inhibitors356 has been established, but the drug activity is limited, and TP53 mutations may occur with long-term administration.357. This evidence concerns the gene TP53 and osteosarcoma.