Abstract
Radioresistance stands as a fundamental barrier that limits the effectiveness of radiotherapy in cancer treatment. Recent evidences suggest that radioresistance is due to tumour repopulation and involves several signalling pathways, including p53/MDM2 interaction. Ionizing radiation induces p53-dependent MDM2 gene transcription that, in turn, inhibits p53 transcriptional activity, favouring its nuclear export and stimulating its degradation. In light of the observation that in many human tumours the inadequate function of p53 is the result of MDM2 over-expression, several authors have considered as an attractive therapeutic strategy to activate p53 signalling in tumours by inhibiting MDM2 activities or p53/MDM2 interaction. We retain that, by preventing the interaction p53/MDM2 with Nutlin, a small molecule that binds at the interface between these two proteins, the effectiveness of ionizing radiation treatment could be improved. Promising results have recently emerged from in vitro studies performed on laryngeal, prostate and lung cancer cell lines treated with Nutlin in combination with ionizing radiation. Based on these findings, we believe that the combined approach Nutlin/ionizing radiation should be further investigated for efficacy on both solid tumours and lymphoproliferative disorders as well as for side effects on normal cells and tissues. Therefore, the purpose of this review is to report the first results obtained by using Nutlins alone or in combination with other therapeutic agents on primary tumour cells, in vitro cell lines or tumour xenografts and to present the most recent advances in the understanding of the molecular mechanisms underlining ionizing radiation cytotoxicity and resistance.
Keywords: p53, MDM2, Nutlins, Ionizing Radiation (IR), Cancer Therapy
Current Pharmaceutical Design
Title: Nutlins and Ionizing Radiation in Cancer Therapy
Volume: 16 Issue: 12
Author(s): Gianna Impicciatore, Silvia Sancilio, Sebastiano Miscia and Roberta Di Pietro
Affiliation:
Keywords: p53, MDM2, Nutlins, Ionizing Radiation (IR), Cancer Therapy
Abstract: Radioresistance stands as a fundamental barrier that limits the effectiveness of radiotherapy in cancer treatment. Recent evidences suggest that radioresistance is due to tumour repopulation and involves several signalling pathways, including p53/MDM2 interaction. Ionizing radiation induces p53-dependent MDM2 gene transcription that, in turn, inhibits p53 transcriptional activity, favouring its nuclear export and stimulating its degradation. In light of the observation that in many human tumours the inadequate function of p53 is the result of MDM2 over-expression, several authors have considered as an attractive therapeutic strategy to activate p53 signalling in tumours by inhibiting MDM2 activities or p53/MDM2 interaction. We retain that, by preventing the interaction p53/MDM2 with Nutlin, a small molecule that binds at the interface between these two proteins, the effectiveness of ionizing radiation treatment could be improved. Promising results have recently emerged from in vitro studies performed on laryngeal, prostate and lung cancer cell lines treated with Nutlin in combination with ionizing radiation. Based on these findings, we believe that the combined approach Nutlin/ionizing radiation should be further investigated for efficacy on both solid tumours and lymphoproliferative disorders as well as for side effects on normal cells and tissues. Therefore, the purpose of this review is to report the first results obtained by using Nutlins alone or in combination with other therapeutic agents on primary tumour cells, in vitro cell lines or tumour xenografts and to present the most recent advances in the understanding of the molecular mechanisms underlining ionizing radiation cytotoxicity and resistance.
Export Options
About this article
Cite this article as:
Impicciatore Gianna, Sancilio Silvia, Miscia Sebastiano and Di Pietro Roberta, Nutlins and Ionizing Radiation in Cancer Therapy, Current Pharmaceutical Design 2010; 16 (12) . https://dx.doi.org/10.2174/138161210791033932
DOI https://dx.doi.org/10.2174/138161210791033932 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Animal Models of Lung Fibrosis
Current Respiratory Medicine Reviews Targeting MAPK Signalling: Prometheus Fire or Pandoras Box?
Current Pharmaceutical Design Structural and Mechanistic Bases of the Anticancer Activity of Natural Aporphinoid Alkaloids
Current Topics in Medicinal Chemistry Promising Anti-Fibrotic Approaches for Future Treatment of Systemic Sclerosis
Current Rheumatology Reviews DNMT Inhibitors in Cancer, Current Treatments and Future Promising Approach: Inhibition of Specific DNMT-Including Complexes
Epigenetic Diagnosis & Therapy (Discontinued) Fused Xanthone Derivatives as Antiproliferative Agents
Anti-Cancer Agents in Medicinal Chemistry Subject Index to Volume 1
Medicinal Chemistry Reviews - Online (Discontinued) Epilogue
Current Pharmaceutical Design Caring for HIV-Infected Patients in the ICU in The Highly Active Antiretroviral Therapy Era
Current HIV Research Molecular Insight and Binding Pattern Analysis of Shikonin as a Potential VEGFR-2 Inhibitor
Current Enzyme Inhibition Chymase Inhibitor As a Novel Therapeutic Strategy for Anti-Vascular Remodeling
Vascular Disease Prevention (Discontinued) A Review of Methods and Tools for Database Integration in Biomedicine
Current Bioinformatics From the Table to the Bedside: Can Food-Derived Sulforaphane be used as a Novel Agent to Treat Leukemia?
Current Cancer Drug Targets Phytochemistry and Pharmacognosy of Naturally Occurring Prenyloxyanthraquinones
Current Drug Targets OPLS-DA as a Suitable Method for Selecting a Set of Gene Transcripts Discriminating RAS- and PTPN11-Mutated Cells in Acute Lymphoblastic Leukaemia
Combinatorial Chemistry & High Throughput Screening Versatile Functions of Heat Shock Factors: It is Not All About Stress
Current Immunology Reviews (Discontinued) Silver Nanoparticles with High Loading Capacity of Amphotericin B: Characterization, Bactericidal and Antifungal Effects
Current Drug Delivery NF-κB, a Potential Therapeutic Target for the Treatment of Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets Synthetic Src-Kinase Domain Inhibitors and Their Structural Requirements
Anti-Cancer Agents in Medicinal Chemistry Natural Compounds and Drug Discovery: Can Cnidarian Venom Play a Role?
Central Nervous System Agents in Medicinal Chemistry