The p53 protein plays a central role in the mechanism of action of epigentic drugs that alter the methylation of cytosine residues in DNA.

The p53 protein plays a central role in the mechanism of action of epigentic drugs that alter the methylation of cytosine residues in DNA.

Oncotarget. 2017 Jan 24;:

Authors: Levine AJ

Abstract
Both normal and cancerous cells, treated with drugs that block cytosine methylation of DNA, are preferentially killed by these drugs when they have p53 mutations and survive if they have a wild type protein. It appears that the wild type p53 protein functions to eliminate cells that undergo large epigenetic alterations and save other cells from death by this drug treatment. This has now been observed in cancerous cells in culture, tumors in animals and tumors in humans. AML cells with p53 mutations in humans treated with decitabine are killed by differentiation or senescense, but then relapse at a high rate becoming drug resistant. The mechanism of resistance to epigenetic drugs in p53 mutant cells, by possibly restoring a wild type p53 gene or restoring a defective p53 pathway, is now an interesting hypothesis to explore.

PMID: 28129641 [PubMed - as supplied by publisher]

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