Restoring p53 function in cancer: novel therapeutic approaches for applying the brakes to tumorigenesis.

p53 tumor suppressor gene encodes for a critical cellular protein that regulate the integrity of the cell and can induce cell cycle arrest and/or apoptosis upon cellular stresses of several origins, including chemotherapeutics. Loss of p53 function occurs in an estimated 50% of all cancers by mutations and deletions while in the presence of wild-type p53 alleles other mechanisms may affect the expression and activity of p53. Alternate mechanisms include methylation of the promoter of p53, deletion or epigenetic inactivation of the p53-positive regulator p14/ARF, elevated expression of the p53 regulators murine double minute 2 (MDM2) and MDMX, or alteration of upstream regulators of p53 such as the kinase ATM.