Dear Colleagues,

In the forty years since the discovery of p53, a large number of studies in basic and applied research have revealed multiple functions of TP53 as a tumor suppressor gene and oncogene, as well as associations between environmental exposures, p53 inactivation and cell transformation. p53 is now recognized to be a master regulator of multiple molecular networks that control cell replication, senescence, DNA repair and epigenetic programs in response to a wide variety of stress stimuli. In the vast majority of human cancers, the TP53 gene is mutated or the p53 protein is functionally inactivated by viral or cellular factors. Specific amino acid substitutions in p53 cause abrogation of tumor suppressive activity, gain of oncogenic functions, extended protein half-life and accumulation in cancer cells.

Comprehensive analysis of the molecular mechanisms involved in abnormal signaling associated with mutant p53 opened the possibility of novel therapeutic strategies that inhibit the mutant protein while rescuing wild type p53 expression. However, many aspects of p53 function remain unknown and this has limited the development of effective therapies for p53-mutant cancers. In this issue, leading scientists in basic and translational research present new insights into the mechanisms of p53 signaling in cancer, as well as strategies to target p53 and related pathways with novel therapeutic agents and immunotherapeutic approaches.

Dr. Maria Lina Tornesello

Guest Editor