Over the past 40 years, the survival of osteosarcoma has stagnated due to a common resistance to neoadjuvant MAP (methotrexate, adriamycin, and platinum) chemotherapy, and increasing genomic and functional studies of osteosarcoma have emerged, expecting to exploit new drug targets.225 Among them, tumor-suppressor genes such as p53 (TP53),226 retinoblastoma (RB),227 PTEN228 et al., were found to be the significant responsible genes in osteosarcoma genesis and its resistance, with recurrent somatic mutations and copy number alterations. Here, TP53 is linked to osteosarcoma.