GOF Mutant p53 in Cancers: A Therapeutic Challenge

• Published in: Cancers Vol. 14; no. 20; p. 5091
• Main Authors: Dolma, Lobsang, Muller, Patricia A. J
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2022; MDPI
• Subjects: Apoptosis; Autophagy; Cancer; Cancer therapies; Care and treatment; Cell cycle; Cell division; Chemoresistance; Chemotherapy; DNA damage; DNA methylation; DNA repair; Drug dosages; gain-of-function; Gene expression; Gene therapy; Gene transfer; GOF; Health aspects; Immunotherapy; Metastases; mutant p53 chemoresistance; Mutants; Mutation; Mutation (Biology); Nucleotide sequence; p53 Protein; Protein expression; Proteins; Review; Senescence; targeted therapy; Tumor proteins; Tumors; United Kingdom
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14205091

TP53 is mutated in the majority of human cancers. Mutations can lead to loss of p53 expression or expression of mutant versions of the p53 protein. These mutant p53 proteins have oncogenic potential. They can inhibit any remaining WTp53 in a dominant negative manner, or they can acquire new functions that promote tumour growth, invasion, metastasis and chemoresistance. In this review we explore some of the mechanisms that make mutant p53 cells resistant to chemotherapy. As mutant p53 tumours are resistant to many traditional chemotherapies, many have sought to explore new ways of targeting mutant p53 tumours and reinstate chemosensitivity. These approaches include targeting of mutant p53 stability, mutant p53 binding partners and downstream pathways, p53 vaccines, restoration of WTp53 function, and WTp53 gene delivery. The current advances and challenges of these strategies are discussed.