We developed a lung tumor model in transgenic mice in which the human mutant p53(273H) is expressed in a lung-specific manner, under the control of the surfactant protein C promoter. Of the 11 treated mice, micro-CT-derived volume changes indicated that five p53-273H mice were responsive to the PRIMA-1 treatment, with an average volume decrease of 93.55 mm3. the PRIMA-1 treated p53-273H mice showed an overall decrease in tumor size, with an average tumor volume fold change of -2.33. The results indicate the activity of PRIMA-1 in lung tumor-bearing P53 mutant transgenics and suggest the potential feasibility of using PRIMA-1 (APR-246) to treat lung cancer.