Abstract
The tumour suppressor p53 is at the centre of a network of regulatory pathways that guard over the continued integrity of the living cell and its progeny after exposure to different forms of stress, particularly those capable of inducing DNA damage. Tumour cells very frequently circumvent this control by disabling the function of p53, or other proteins in the p53 network, through mutation. Here we review the different therapeutic strategies that have been adopted to exploit common neoplastic aberrations in the p53 pathways. We emphasise in particular those approaches where modulation with pharmaceutical agents has already shown some promise, including pharmacological rescue of mutant p53, modulation of the protein-protein interaction between p53 and one of its negative regulators, Mdm2, as well as interference with downstream targets.
Keywords: p53-Mdm2 Pathway, protein
Mini-Reviews in Medicinal Chemistry
Title: The p53-Mdm2 Pathway: Targets for the Development of New Anticancer Therapeutics
Volume: 3 Issue: 3
Author(s): Daniella I. Zheleva, David P. Lane and Peter M. Fischer
Affiliation:
Keywords: p53-Mdm2 Pathway, protein
Abstract: The tumour suppressor p53 is at the centre of a network of regulatory pathways that guard over the continued integrity of the living cell and its progeny after exposure to different forms of stress, particularly those capable of inducing DNA damage. Tumour cells very frequently circumvent this control by disabling the function of p53, or other proteins in the p53 network, through mutation. Here we review the different therapeutic strategies that have been adopted to exploit common neoplastic aberrations in the p53 pathways. We emphasise in particular those approaches where modulation with pharmaceutical agents has already shown some promise, including pharmacological rescue of mutant p53, modulation of the protein-protein interaction between p53 and one of its negative regulators, Mdm2, as well as interference with downstream targets.
Export Options
About this article
Cite this article as:
Zheleva I. Daniella, Lane P. David and Fischer M. Peter, The p53-Mdm2 Pathway: Targets for the Development of New Anticancer Therapeutics, Mini-Reviews in Medicinal Chemistry 2003; 3 (3) . https://dx.doi.org/10.2174/1389557033488178
DOI https://dx.doi.org/10.2174/1389557033488178 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
-
Perspectives of Protein Kinase C (PKC) Inhibitors as Anti-Cancer Agents
Mini-Reviews in Medicinal Chemistry Genomic Sequencing of Key Genes in Mouse Pancreatic Cancer Cells
Current Molecular Medicine HPV Pathway Profiling: HPV Related Cervical Dysplasia and Carcinoma Studies
Current Pharmaceutical Design The Neurotrophic and Antiangiogenic Functions of PEDF: A Reflection of its Variable Phosphorylation States
Current Genomics Tea (Camellia sinensis (L.)): A Putative Anticancer Agent in Bladder Carcinoma?
Anti-Cancer Agents in Medicinal Chemistry Nanoparticles Mediated Target-specific Drug Delivery in Prostate Cancer: An In-depth Review
Current Medicinal Chemistry Cyclin-Dependent Kinase as a Novel Therapeutic Target: An Endless Story
Current Chemical Biology From Peptides to Small Molecules: An Intriguing but Intricated Way to New Drugs
Current Medicinal Chemistry Store-Dependent Ca2+ Entry in Endothelial Progenitor Cells As a Perspective Tool to Enhance Cell-Based Therapy and Adverse Tumour Vascularization
Current Medicinal Chemistry Biochemical Mechanisms of Cisplatin Cytotoxicity
Anti-Cancer Agents in Medicinal Chemistry Seocalcitol (EB 1089) A Vitamin D Analogue of Anti-cancer Potential. Background, Design, Synthesis, Pre-clinical and Clinical Evaluation
Current Pharmaceutical Design Immunokinases, a Novel Class of Immunotherapeutics for Targeted Cancer Therapy
Current Pharmaceutical Design Ras-Induced Senescence and its Physiological Relevance in Cancer
Current Cancer Drug Targets Gliomas: New Perspectives in Diagnosis, Treatment and Prognosis
Current Topics in Medicinal Chemistry Therapeutic Polycomb Targeting in Human Cancer
Recent Patents on Regenerative Medicine Combining Oncolytic Virotherapy and Cytotoxic Therapies to Fight Cancer
Current Pharmaceutical Design MicroRNA-7 Regulates Insulin Signaling Pathway by Targeting IRS1, IRS2, and RAF1 Genes in Gestational Diabetes Mellitus
MicroRNA Molecular Pathways Associated with Aggressiveness of Papillary Thyroid Cancer
Current Genomics Oncolytic Viruses Driven by Tumor-Specific Promoters
Current Cancer Drug Targets Perinatal Management of Fetal Tumors
Current Pediatric Reviews