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)
Zawacka-Pankau, J.E. The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy-Drug Repurposing. Cancers2020, 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.
Zawacka-Pankau, J.E. The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy-Drug Repurposing. Cancers2020, 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.
Abstract
p53 and p73 are critical tumor suppressors often inactivated in human cancers throughvarious mechanisms. Owing to high structural homology, the proteins have many commonfunctions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53is known as the ‘guardian of the genome’ and together with p73 form a barrier against cancerdevelopment and progression. The TP53 is mutated in more than 50% of all human cancers and thegermline mutations in TP53 predispose to the early onset of multiple tumors in Li-FraumeniSyndrome (LFS), the inherited cancer predisposition. In cancers where TP53 gene is intact, p53 isdegraded. Despite the ongoing efforts, the treatment of cancers remains challenging. This is due tolate diagnoses, the toxicity of current standard of care and marginal benefit of newly approvedtherapies. Presently, the endeavours focus on reactivating p53 exclusively, neglecting the potentialof the restoration of p73 protein for cancer eradication. Taken that several small moleculesreactivating p53 failed in clinical trials, there is a need to develop new treatments targeting p53proteins in cancer. This review outlines the most advanced strategies to reactivate p53 and p73 anddescribes drug repurposing approaches for the efficient reinstatement of the p53 proteins for cancertherapy.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Commenter: Joanna Zawacka-Pankau
Commenter's Conflict of Interests: Author