Resistance to MDM2-p53 binding antagonists has been suggested to be acquired by prolonged exposure of cells to sub-lethal doses through de novo inactivating TP53 mutations or selection of pre-existing subclones of TP53 mutant cells that might be present as a result of cancer cell genomic instability and tumor heterogeneity [22, 23]. This evidence concerns the gene TP53 and neoplasm.