Abstract
p53 is one of the most important tumor suppressor genes that is frequently mutated in human cancers. Generally, p53 functions as a transcription factor that is stabilized and activated by various genotoxic and cellular stress signals, such as DNA damage, hypoxia, oncogene activation and nutrient deprivation, consequently leading to cell cycle arrest, apoptosis, senescence and metabolic adaptation. p53 not only becomes functionally deficient in most cancers, but not infrequently mutant p53 also acquires dominant negative activity and oncogenic properties. p53 has remained an attractive target for cancer therapy. Strategies targeting p53 have been developed including gene therapy to restore p53 function, inhibition of p53-MDM2 interaction, restoration of mutant p53 to wild-type p53, targeting p53 family proteins, eliminating mutant p53, as well as p53-based vaccines. Some of these p53-targeted therapies have entered clinical trials. We discuss the therapeutic potential of p53, with particular focus on the therapeutic strategies to rescue p53 inactivation in human cancers. In addition, we discuss the challenges of p53-targeted therapy and new opportunities for the future.
Keywords: Tumor suppressor, p53, mutant p53, p53-targeted therapy, restoration of p53, MDM2, p53 family protein.
Current Drug Targets
Title:Targeting Tumor Suppressor p53 for Cancer Therapy: Strategies, Challenges and Opportunities
Volume: 15 Issue: 1
Author(s): Bo Hong, A. Pieter J. van den Heuvel, Varun V. Prabhu, Shengliang Zhang and Wafik S. El-Deiry
Affiliation:
Keywords: Tumor suppressor, p53, mutant p53, p53-targeted therapy, restoration of p53, MDM2, p53 family protein.
Abstract: p53 is one of the most important tumor suppressor genes that is frequently mutated in human cancers. Generally, p53 functions as a transcription factor that is stabilized and activated by various genotoxic and cellular stress signals, such as DNA damage, hypoxia, oncogene activation and nutrient deprivation, consequently leading to cell cycle arrest, apoptosis, senescence and metabolic adaptation. p53 not only becomes functionally deficient in most cancers, but not infrequently mutant p53 also acquires dominant negative activity and oncogenic properties. p53 has remained an attractive target for cancer therapy. Strategies targeting p53 have been developed including gene therapy to restore p53 function, inhibition of p53-MDM2 interaction, restoration of mutant p53 to wild-type p53, targeting p53 family proteins, eliminating mutant p53, as well as p53-based vaccines. Some of these p53-targeted therapies have entered clinical trials. We discuss the therapeutic potential of p53, with particular focus on the therapeutic strategies to rescue p53 inactivation in human cancers. In addition, we discuss the challenges of p53-targeted therapy and new opportunities for the future.
Export Options
About this article
Cite this article as:
Hong Bo, Heuvel Pieter J. van den A., Prabhu V. Varun, Zhang Shengliang and El-Deiry S. Wafik, Targeting Tumor Suppressor p53 for Cancer Therapy: Strategies, Challenges and Opportunities, Current Drug Targets 2014; 15 (1) . https://dx.doi.org/10.2174/1389450114666140106101412
DOI https://dx.doi.org/10.2174/1389450114666140106101412 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
Related Articles
-
Management of Locally Advanced Cancer Cervix an Indian Perspective
Reviews on Recent Clinical Trials The Anti-Oxidant Properties of Isothiocyanates: A Review
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Behavioral Decision Research Intervention Reduces Risky Sexual Behavior
Current HIV Research Brain Tumor-Related Epilepsy
Current Neuropharmacology LPA and its Analogs-Attractive Tools for Elucidation of LPA Biology and Drug Development
Current Medicinal Chemistry Prediction of MicroRNA–disease Associations by Matrix Completion
Current Proteomics Recent Insights into COVID-19 in Children and Clinical Recommendations
Current Pediatric Reviews Purine Ionotropic (P2X) Receptors
Current Pharmaceutical Design Polyphenols as Potential Therapeutics for Pain and Inflammation in Spinal Cord Injury
Current Molecular Pharmacology Targeting Post-Ejaculation Sperm for Value-Added Contraception
Current Molecular Pharmacology AAVs Anatomy: Roadmap for Optimizing Vectors for Translational Success
Current Gene Therapy Pharmacotherapy for Obesity
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Molecular Mechanisms Underlying St. Johns Wort Drug Interactions
Current Drug Metabolism An Update on Developments in Female Hormonal Contraception
Current Women`s Health Reviews Drug Targeting Strategies for Photodynamic Therapy
Anti-Cancer Agents in Medicinal Chemistry Genetic and Modifying Factors that Determine the Risk of Brain Tumors
Central Nervous System Agents in Medicinal Chemistry Dimer and Tetramer of Gallic Acid: Facile Synthesis, Antioxidant and Antiproliferative Activities
Letters in Drug Design & Discovery The Impacts of Non-coding RNAs and N<sup>6</sup>-Methyladenosine on Cancer: Past, Present and Future
Current Cancer Drug Targets The Applications of Targeting Anti-Cancer Agents in Cancer Therapeutics
Anti-Cancer Agents in Medicinal Chemistry Zinc Dependent Histone Deacetylase Inhibitors in Cancer Therapeutics: Recent Update
Current Medicinal Chemistry