Should mutant TP53 be targeted for cancer therapy?

Abstract

Mutations in the TP53 tumour suppressor gene are found in ~50% of human cancers [1–6]. TP53 functions as a transcription factor that directly regulates the expression of ~500 genes, some of them involved in cell cycle arrest/cell senescence, apoptotic cell death or DNA damage repair, i.e. the cellular responses that together prevent tumorigenesis [1–6]. Defects in TP53 function not only cause tumour development but also impair the response of malignant cells to anti-cancer drugs, particularly those that induce DNA damage [1–6]. Most mutations in TP53 in human cancers cause a single amino acid substitution, usually within the DNA binding domain of the TP53 protein. These mutant TP53 proteins ..