Abstract
p53 and its related genes, p73 and p63, are members of the p53 gene family. While p53 is the most frequently mutated gene in human tumors, p73 and p63 are rarely mutated or lost in cancers. Although p53-deficient cancer cells are often less responsive to chemotherapy, they are not completely drug resistant, suggesting that other apoptotic pathways are at work. Interestingly, several studies have shown that p73, and more recently p63, are involved in cellular response to cancer therapy, while others have indicated that p63 and p73 are required for p53-induced apoptosis, delineating functional interplay between p53 family members. The latest reports in this field have established that Nutlin-3, a selective inhibitor of p53-MDM2 interaction, disrupts p73-MDM2 and enhances p73 function in p53-null cells, and that a p53- derived peptide that targets iASPP — a common negative regulator of p53 family members — can trigger cell death via a p73-dependant mechanism. It has also been shown that a small-molecule RETRA suppressed mutant p53-bearing cancers cells through a p73-dependant salvage pathway. Finally, there is increasing evidence that cleaved fragments of p53, p63 and p73 are involved in apoptosis and it remains to be determined whether or not pro-forms of the p53 family play an apoptotic role mediated by cleavage. This review will highlight research into drugs and mechanisms that activate p63 and p73, since these proteins are not mutated in cancers and as such are potential candidates for replacing p53 in p53-deficient cells. It will therefore focus on recent findings in the search for pathways and molecules capable of modulating p53 family protein activities and restoring response to cancer therapy, particularly in tumors bearing p53 mutations.
Keywords: p53, p73, p53 rescuing, MDM2, chemotherapy, apoptosis
Current Medicinal Chemistry
Title: P53 Family: At the Crossroads in Cancer Therapy
Volume: 16 Issue: 32
Author(s): S. Alsafadi, S. Tourpin, F. Andre, G. Vassal and J-C. Ahomadegbe
Affiliation:
Keywords: p53, p73, p53 rescuing, MDM2, chemotherapy, apoptosis
Abstract: p53 and its related genes, p73 and p63, are members of the p53 gene family. While p53 is the most frequently mutated gene in human tumors, p73 and p63 are rarely mutated or lost in cancers. Although p53-deficient cancer cells are often less responsive to chemotherapy, they are not completely drug resistant, suggesting that other apoptotic pathways are at work. Interestingly, several studies have shown that p73, and more recently p63, are involved in cellular response to cancer therapy, while others have indicated that p63 and p73 are required for p53-induced apoptosis, delineating functional interplay between p53 family members. The latest reports in this field have established that Nutlin-3, a selective inhibitor of p53-MDM2 interaction, disrupts p73-MDM2 and enhances p73 function in p53-null cells, and that a p53- derived peptide that targets iASPP — a common negative regulator of p53 family members — can trigger cell death via a p73-dependant mechanism. It has also been shown that a small-molecule RETRA suppressed mutant p53-bearing cancers cells through a p73-dependant salvage pathway. Finally, there is increasing evidence that cleaved fragments of p53, p63 and p73 are involved in apoptosis and it remains to be determined whether or not pro-forms of the p53 family play an apoptotic role mediated by cleavage. This review will highlight research into drugs and mechanisms that activate p63 and p73, since these proteins are not mutated in cancers and as such are potential candidates for replacing p53 in p53-deficient cells. It will therefore focus on recent findings in the search for pathways and molecules capable of modulating p53 family protein activities and restoring response to cancer therapy, particularly in tumors bearing p53 mutations.
Export Options
About this article
Cite this article as:
Alsafadi S., Tourpin S., Andre F., Vassal G. and Ahomadegbe J-C., P53 Family: At the Crossroads in Cancer Therapy, Current Medicinal Chemistry 2009; 16 (32) . https://dx.doi.org/10.2174/092986709789578196
DOI https://dx.doi.org/10.2174/092986709789578196 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Current and Potential Treatments for Cervical Cancer
Current Cancer Drug Targets Role of the Akt Pathway in Prostate Cancer
Current Cancer Drug Targets Radiolabeling Methods and Nuclear Imaging Techniques in the Design of New Polymeric Carriers for Cancer Therapy
Current Applied Polymer Science NAD Precursors, Mitochondria Targeting Compounds and ADP-Ribosylation Inhibitors in Treatment of Inflammatory Diseases and Cancer
Current Medicinal Chemistry High Expression of MYL9 Indicates Poor Clinical Prognosis of Epithelial Ovarian Cancer
Recent Patents on Anti-Cancer Drug Discovery Challenges in the Correct Assessment of a Case of Aggressive Thyroid Carcinoma with Synchronous Breast Cancer: A Case Report and Review of the Literature of Essential Role of Radiopharmaceuticals
Current Radiopharmaceuticals Improvement of Tumor Localization of Photosensitizers for Photodynamic Therapy and Its Application for Tumor Diagnosis
Current Topics in Medicinal Chemistry Screening for Infectious Diseases During Pregnancy: Which Test and Which Situation
Current Women`s Health Reviews Review of the Biological Activity of Maslinic Acid
Current Drug Targets An Update of Radiolabeled Bombesin Analogs for Gastrin-Releasing Peptide Receptor Targeting
Current Pharmaceutical Design DNA Intercalators in Cancer Therapy: Organic and Inorganic Drugs and Their Spectroscopic Tools of Analysis
Mini-Reviews in Medicinal Chemistry Subject Index to Volume 3
Current Gene Therapy The Involvement of ERCC2/XPD and ERCC6/CSB Wild Type Alleles in Protection Against Aging and Cancer
Current Aging Science Novel Therapeutic Strategies Against Cancer: Marine-derived Drugs May Be the Answer?
Anti-Cancer Agents in Medicinal Chemistry Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein 1: Recent Developments Concerning Substrates and Inhibitors of a Promising Therapeutic Target
Current Medicinal Chemistry Microarrays and Colon Cancer in the Road for Translational Medicine
Current Bioinformatics Alpha-Helical Cationic Anticancer Peptides: A Promising Candidate for Novel Anticancer Drugs
Mini-Reviews in Medicinal Chemistry Cucurbitacin IIb from Ibervillea sonorae Induces Apoptosis and Cell Cycle Arrest via STAT3 Inhibition
Anti-Cancer Agents in Medicinal Chemistry Synthesis and Evaluation of 99mTc Chelate-conjugated Bevacizumab
Current Radiopharmaceuticals Botulinum Toxin a in Prostate Disease: A Venom from Bench to Bed-Side
Current Drug Delivery