TP53 273H

Recently, the FDA granted breakthrough therapy designation to the PRIMA-1 methylated analog, APR-246 in combination with azacytidine for the treatment of patients with myelodysplastic syndromes and a TP53 mutation. PRIMA 1 therapy results in antitumor activity against P53 mutant lung tumors. However, the presence of K-ras co-mutation is a significant resistance factor. Combination of APR-246 and K-ras inhibitor therapy would be needed to overcome this resistance.

PRIMA-1 methylated analog, PRIMA-1Met (APR-246, Eprenetapopt) have been used in clinical trials to target cancers containing mutant TP53...This difference is due to model specific expression. Further investigation is needed to better understand the effects of PRIMA-1 in regulation of micro-RNA expression in the treatment of lung cancers containing mutant p53.

The results of the study indicated a significant reduction in tumor size in the mice treated with PRIMA-1, based on micro-CT images. Contrary to this finding, an increased average fold change was seen in the control group, indicating an overall average increase in tumor volume. 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.