Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy - Drug Repurposing

Version 1 : Received: 31 August 2020 / Approved: 31 August 2020 / Online: 31 August 2020 (17:55:15 CEST)
Version 2 : Received: 14 September 2020 / Approved: 17 September 2020 / Online: 17 September 2020 (07:23:37 CEST)

A peer-reviewed article of this Preprint also exists.

Zawacka-Pankau, J.E. The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy-Drug Repurposing. Cancers 2020, 12, 2717. Zawacka-Pankau, J.E. The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy-Drug Repurposing. Cancers 2020, 12, 2717.

Journal reference: Cancers 2020, 12, 2717
DOI: 10.3390/cancers12092717

Abstract

p53 and p73 are critical tumor suppressors often inactivated in human cancers through various mechanisms. Owing to high structural homology, the proteins have many common functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the ‘guardian of the genome’ and together with p73 form a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li-Fraumeni Syndrome (LFS), the inherited cancer predisposition. In cancers where TP53 gene is intact, p53 is degraded. Despite the ongoing efforts, the treatment of cancers remains challenging. This is due to late diagnoses, the toxicity of current standard of care and marginal benefit of newly approved therapies. Presently, the endeavours focus on reactivating p53 exclusively, neglecting the potential of the restoration of p73 protein for cancer eradication. Taken that several small molecules reactivating p53 failed in clinical trials, there is a need to develop new treatments targeting p53 proteins in cancer. This review outlines the most advanced strategies to reactivate p53 and p73 and describes drug repurposing approaches for the efficient reinstatement of the p53 proteins for cancer therapy.

Subject Areas

p53; p73; MDM2; MDMX; tumor suppressor; drug repurposing; aspirin; protoporphyrin IX; verteporfin

Comments (1)

Comment 1
Received: 17 September 2020
Commenter: Joanna Zawacka-Pankau
Commenter's Conflict of Interests: Author
Comment: This version includes new sections and has a new Table 1.
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