USE OF FATOSTATIN FOR TREATING CANCER HAVING A p53 MUTATION

摘要

Fatostatin, a recently described inhibitor of SREBP activation, significantly reduces the level of mutant p53 binding to the HMG-CoA reductase gene promoter. Further, fatostatin treatment had a dramatic effect on normalizing the abnormal 3D morphology of 3 strains of breast cancer cells: MDA-468 cells, MDA-231 cells, and SKBR3 cells. The results show a functional interaction with SREBPs as being critical for mutant p53-mediated upregulation of the mevalonate pathway genes. At a clinical level, inhibition of the mevalonate pathway, either alone or in combination with other therapies, offers a novel, safe and much needed therapeutic option for tumors bearing mutant p53.

主权项

1. A method comprising:
(a) identifying a subject having cancer, precancerous cells, or a benign tumor that has a mutated p53 gene or that expresses a mutant p53 protein or an mRNA encoding a mutant p53 protein; and (b) administering to the subject a therapeutically effective amount of an SREBP cleavage activating protein inhibitor, in an amount that reduces or eliminates the cancer, the precancerous cells, or the benign tumor.