Our findings showing that the p53β/γ isoforms are MDM2 resistant and that NMD inhibition restores p53 pathway, increases radiation sensitivity, reduces tumor cell colony forming ability, and impairs tumor growth in MDM2 overexpressing tumor cells signify the clinical relevance of NMD inhibition for this particular subgroup and also other smaller p53-deficient subgroups (e.g., p53 mutations downstream of exon 9) for which this approach could be used. Here, MDM2 is linked to neoplasm.