P53 and It's Applications in Cancer Therapy

Abstract

P53 is a tumour suppressor protein encoded by the TP53 gene, which is one of the most commonly mutated gene in human and animal cancers. Missense Mutation of the p53 gene is the most prevalent genetic abnormalities which gives rise to full length p53 containing single amino acid substitution within the sequence-specific DNA binding domain (|Greenblatt et al., 1994)14. p53 plays anti-cancer role, through several mechanisms namely by activating DNA repair, initiating apoptosis and inducing growth arrest. By managing the DNA damage, p53 gene plays an important role in maintaining integrity and stability of the genome and therefore, it has been described as "the guardian of the genome". Restoring p53 function is a major step in the treatment of many cancers by following different strategies like, gene replacement therapy using wild-type p53, reactivation of p53 function, inhibition of p53-Mdm2 interaction etc. Advexin is an Adeno-p53 vector, recognized as an orphan drug by USA, Food and Drug administration in 2003, provides delivery of wild-type p53 to cancer cells and demonstrates anticancer activity following adequate expression of p53 (Nemunaitis and Nemunaitis, 2008)27. Similarly, MI-319 restores p53 functions and increases the life span of orally treated follicular lymphoma bearing animals (Mohammad et al., 2009)25. These strategies of p53-based cancer therapy differ greatly between themselves both in the mode of action and the degree of success seen in experimental models. Cancer therapy based around p53 proves to be more efficacious, especially in terms of specificity. But the innovation of successful p53-based cancer therapies is only limited by our understanding of p53 biology and the creative use of such knowledge. In future, p53-based cancer therapy can be a valuable option for the treatment of a variety of tumours in human as well as animals.