Abstract
Nutlin-3 is a small molecule inhibitor of the MDM2/p53 interaction, which leads to the non-genotoxic p53 stabilization, activation of cell cycle arrest and apoptosis pathways. A series of recent studies have strengthened the concept that selective, non-genotoxic p53 activation by Nutlin-3 might represent an alternative to the current cytotoxic chemotherapy, in particular for pediatric tumors and for hematological malignancies, which retain a high percentage of p53wild-type status at diagnosis. Like most other drugs employed in cancer therapy, it will be unlikely that Nutlin-3 will be used as a monotherapy. In this respect, Nutlin-3 shows a synergistic cytotoxic effect when used in combination with innovative drugs, such as TRAIL or bortozemib. Although Nutlin-3 is currently in phase I clinical trial for the treatment of retinoblastoma, its effects on normal tissues and cell types remain largely to be determined and will require further investigation in the future years.
Keywords: Pediatric malignancies, hematological malignancies, p53 pathway, apoptosis, senescence, therapeutic combinations, Nutlin-3, MDM2, HDM2, PEDIATRIC TUMORS, chemotherapy, malignancies, P-gp, p53-independent, leukemia, synergistic, endothelial, autophagic, pharmacokinetics
Current Pharmaceutical Design
Title: Recent Advances in the Therapeutic Perspectives of Nutlin-3
Volume: 17 Issue: 6
Author(s): Paola Secchiero, Raffaella Bosco, Claudio Celeghini and Giorgio Zauli
Affiliation:
Keywords: Pediatric malignancies, hematological malignancies, p53 pathway, apoptosis, senescence, therapeutic combinations, Nutlin-3, MDM2, HDM2, PEDIATRIC TUMORS, chemotherapy, malignancies, P-gp, p53-independent, leukemia, synergistic, endothelial, autophagic, pharmacokinetics
Abstract: Nutlin-3 is a small molecule inhibitor of the MDM2/p53 interaction, which leads to the non-genotoxic p53 stabilization, activation of cell cycle arrest and apoptosis pathways. A series of recent studies have strengthened the concept that selective, non-genotoxic p53 activation by Nutlin-3 might represent an alternative to the current cytotoxic chemotherapy, in particular for pediatric tumors and for hematological malignancies, which retain a high percentage of p53wild-type status at diagnosis. Like most other drugs employed in cancer therapy, it will be unlikely that Nutlin-3 will be used as a monotherapy. In this respect, Nutlin-3 shows a synergistic cytotoxic effect when used in combination with innovative drugs, such as TRAIL or bortozemib. Although Nutlin-3 is currently in phase I clinical trial for the treatment of retinoblastoma, its effects on normal tissues and cell types remain largely to be determined and will require further investigation in the future years.
Export Options
About this article
Cite this article as:
Secchiero Paola, Bosco Raffaella, Celeghini Claudio and Zauli Giorgio, Recent Advances in the Therapeutic Perspectives of Nutlin-3, Current Pharmaceutical Design 2011; 17 (6) . https://dx.doi.org/10.2174/138161211795222586
DOI https://dx.doi.org/10.2174/138161211795222586 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Adenoviral Vectors for Cancer Gene Therapy
Current Genomics Cyclin-Dependent Kinase as a Novel Therapeutic Target: An Endless Story
Current Chemical Biology Role of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Different Disease States: Recent Updates
Current Medicinal Chemistry Mammalian Target of Rapamycin (mTOR) Inhibitors as Anti-Cancer Agents
Current Cancer Drug Targets Current Progress of Reelin in Development, Inflammation and Tissue Remodeling: From Nervous to Visual Systems
Current Molecular Medicine The Urokinase Plasminogen Activator System: A Target for Anti-Cancer Therapy
Current Cancer Drug Targets Metastasis Suppressors: Basic and Translational Advances
Current Pharmaceutical Biotechnology Sorbinil, an Aldose Reductase Inhibitor, in Fighting Against Diabetic Complications
Medicinal Chemistry Pharmacology and Therapeutic Applications of Enediyne Antitumor Antibiotics
Current Molecular Pharmacology Human Platelet Acetylcholinesterase Inhibition by Cyclophosphamide: A Combined Experimental and Computational Approach
CNS & Neurological Disorders - Drug Targets Tachykinins and their Receptors in Human Malignancies
Current Drug Targets The Role of Apoptosis in Cancer Development and Treatment: Focusing on the Development and Treatment of Hematologic Malignancies
Current Pharmaceutical Design Four Major Factors Regulate Phosphatidylinositol 3-kinase Signaling Pathway in Cancers Induced by Infection of Human Papillomaviruses
Current Medicinal Chemistry DNA Methylation, An Epigenetic Mode of Gene Expression Regulation in Reproductive Science
Current Pharmaceutical Design Sirtuins: Novel Players in Male Reproductive Health
Current Medicinal Chemistry Advances in the Development of Non-Human Viral DNA-Vectors for Gene Delivery
Current Gene Therapy Oxidative Stress in Tumor Angiogenesis - Therapeutic Targets
Current Pharmaceutical Design The Development of MetAP-2 Inhibitors in Cancer Treatment
Current Medicinal Chemistry Deubiquitinating Enzymes as Therapeutic Targets in Cancer
Current Pharmaceutical Design Dietary and Plant Polyphenols Exert Neuroprotective Effects and Improve Cognitive Function in Cerebral Ischemia
Recent Patents on Food, Nutrition & Agriculture