About this Research Topic

Background

The transcription factor p53 is one of the most widely studied tumor suppressor genes and has been referred to as the “guardian of the genome” due to its pivotal role in the regulation of signaling pathways linked to cell survival, DNA repair, apoptosis, senescence, antioxidant functions, and energy metabolism.

Mutations in the TP53 gene occur in more than 50% of human cancers. Many of these are missense mutations in the p53 DNA Binding Domain (DBD) that encodes for mutant p53 isoforms, showing new oncogenic abilities referred to as the gain-of-function (GOF). GOF mutations sustain tumor progression through the regulation of a complex set of signaling pathways associated to i) adaptive metabolic switch in responses to cancer-related stressing conditions, ii) reduced response to chemotherapy and iii) promotion of migration, invasion, and metastasis.

Cancer cells expressing mutant p53 proteins show high levels of oxidative stress, genomic instability, metabolic rewiring, drug resistance and enhanced metastatic potential. Hence, novel approaches aimed to inhibit the expression of mutant p53 proteins could represent a valid therapeutic approach for patients bearing mutant p53 associated cancer. The strategies that are usually employed for targeting mutant p53 includes a) reactivation or restoration of wild-type p53 activity and elimination of mutant p53; (b) destabilization of the oncogenic mutant p53 protein; and (c) inhibiting the downstream signaling resulting from mutant p53 gain-of-function. Moreover, recent advances in nanotechnology have led to the development of different nanomaterials that can be employed to improve the delivery and the biodistribution of drugs, peptides or nucleic acids, and may represent innovative strategies against mutant p53 associated cancers.

The goal of this Research Topic is to provide an overview on the molecular mechanisms underlying cancer progression driven by mutant p53 proteins as well as the identification of novel strategies aimed to counteract mutant p53 functions for personalized cancer treatments. We encourage the submission of original articles and reviews in the wide field of mutant p53 biology and/or novel approaches aimed at targeting oncogenic mutant p53 isoforms.

This Research Topic focuses on novel molecular mechanisms related to mutant p53 in tumors as well as on the discovery and characterization of innovative therapeutic approaches and nanomedicines based on the inhibition of mutant p53 proteins or the oncogenic signaling downstream, and the related underlying molecular mechanisms.

Keywords: mutant p53, TP53, cancer progression, cancer therapy, signaling pathways

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