p53: From Fundamental Biology to Clinical Applications in Cancer

Simple Summary p53 tumour suppressor gene is the most altered in cancer. Several decades of research have established that it is of pivotal importance in prompting neoplastic phenomena, including cancer initiation and progression. However, it has crucial functions for cellular life. Knowledge and awareness about these multifaceted properties should be part of the cultural background of all scientists. In this review, we describe and discuss the multifaceted roles of p53, from its discovery to clinical applications in cancer therapy. p53 tumour suppressor gene is our major barrier against neoplastic transformation. It is involved in many cellular functions, including cell cycle arrest, senescence, DNA repair, apoptosis, autophagy, cell metabolism, ferroptosis, immune system regulation, generation of reactive oxygen species, mitochondrial function, global regulation of gene expression, miRNAs, etc. Its crucial importance is denounced by the high percentage of amino acid sequence identity between very different species (Homo sapiens, Drosophila melanogaster, Rattus norvegicus, Danio rerio, Canis lupus familiaris, Gekko japonicus). Many of its activities allowed life on Earth (e.g., repair from radiation-induced DNA damage) and directly contribute to its tumour suppressor function. In this review, we provide paramount information on p53, from its discovery, which is an interesting paradigm of science evolution, to potential clinical applications in anti-cancer treatment. The description of the fundamental biology of p53 is enriched by specific information on the structure and function of the protein as well by tumour/host evolutionistic perspectives of its role.