Abstract
Retinoblastoma is the third most common form of cancer in infants, and metastatic retinoblastoma is lethal in approximately 90% of cases. Early detection and aggressive therapy has resulted in a 95% probability of survival for retinoblastoma patients in the United States. However, the United States only represents 3-4% of the retinoblastoma cases worldwide. The majority of children diagnosed with retinoblastoma each year live in developing countries where the probability of survival is closer to 50%. This difference in survival rates reflects poor early detection rates and limited resources for the aggressive therapy necessary to treat retinoblastoma and manage the side effects associated with broad-spectrum systemic chemotherapy in young children. In order to have the most significant impact on retinoblastoma treatment in the United States and worldwide, current efforts have focused on local delivery of targeted chemotherapy. In this review, we summarize recent data showing that the p53 pathway is inactivated in 75% of retinoblastoma patients due to extra copies of the MDM2 and MDMX genes. A small molecule inhibitor of MDM2 called nutlin-3 can induce p53-mediated cell death in retinoblastoma cells. Subconjunctival delivery of nutlin-3 in preclinical models of retinoblastoma confirmed the efficacy of this approach in vivo. The advantage of local application of targeted chemotherapeutic agents such as nutlin-3 is that greater intraocular drug concentrations can be achieved without the side effects associated with systemic broad-spectrum chemotherapy. We propose that subconjunctival administration of targeted chemotherapy may be the best treatment option for children with retinoblastoma in the United States and throughout the developing world because it provides greater tumor response without the costs and complications associated with current treatment protocols.
Current Cancer Drug Targets
Title: Targeting MDM2 and MDMX in Retinoblastoma
Volume: 7 Issue: 7
Author(s): Nikia A. Laurie, Chie Schin-Shih and Michael A. Dyer
Affiliation:
Keywords: Nutlin-3, MDMX, MDM2, p53, topotecan
Abstract: Retinoblastoma is the third most common form of cancer in infants, and metastatic retinoblastoma is lethal in approximately 90% of cases. Early detection and aggressive therapy has resulted in a 95% probability of survival for retinoblastoma patients in the United States. However, the United States only represents 3-4% of the retinoblastoma cases worldwide. The majority of children diagnosed with retinoblastoma each year live in developing countries where the probability of survival is closer to 50%. This difference in survival rates reflects poor early detection rates and limited resources for the aggressive therapy necessary to treat retinoblastoma and manage the side effects associated with broad-spectrum systemic chemotherapy in young children. In order to have the most significant impact on retinoblastoma treatment in the United States and worldwide, current efforts have focused on local delivery of targeted chemotherapy. In this review, we summarize recent data showing that the p53 pathway is inactivated in 75% of retinoblastoma patients due to extra copies of the MDM2 and MDMX genes. A small molecule inhibitor of MDM2 called nutlin-3 can induce p53-mediated cell death in retinoblastoma cells. Subconjunctival delivery of nutlin-3 in preclinical models of retinoblastoma confirmed the efficacy of this approach in vivo. The advantage of local application of targeted chemotherapeutic agents such as nutlin-3 is that greater intraocular drug concentrations can be achieved without the side effects associated with systemic broad-spectrum chemotherapy. We propose that subconjunctival administration of targeted chemotherapy may be the best treatment option for children with retinoblastoma in the United States and throughout the developing world because it provides greater tumor response without the costs and complications associated with current treatment protocols.
Export Options
About this article
Cite this article as:
Laurie A. Nikia, Schin-Shih Chie and Dyer A. Michael, Targeting MDM2 and MDMX in Retinoblastoma, Current Cancer Drug Targets 2007; 7 (7) . https://dx.doi.org/10.2174/156800907782418266
DOI https://dx.doi.org/10.2174/156800907782418266 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Innovative Cancer Drug Targets: A New Horizon in Oncology
Cancer remains one of the most challenging diseases, with its complexity and adaptability necessitating continuous research efforts into more effective and targeted therapeutic approaches. Recent years have witnessed significant progress in understanding the molecular and genetic basis of cancer, leading to the identification of novel drug targets. These include, but ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
![](/images/wayfinder.jpg)
- 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
-
Targeting Phospholipase D-mediated Survival Signals in Cancer
Current Signal Transduction Therapy Prostate Cancer Prevention by Silibinin
Current Cancer Drug Targets Molecular Approaches Target to Immunotherapy for HPV-Associated Cancers
Current Cancer Drug Targets Sirtuin Modulators: Mechanisms and Potential Clinical Implications
Current Medicinal Chemistry Pathobiology and Prevention of Cancer Chemotherapy-Induced Bone Growth Arrest, Bone Loss, and Osteonecrosis
Current Molecular Medicine Small and Long Non-Coding RNAs: Novel Targets in Perspective Cancer Therapy
Current Genomics Targeted Theranostics Against Solid Cancer Using Metal Bond Milk Protein and Aptamers
Current Topics in Medicinal Chemistry Nanomaterials and Stem Cell Differentiation Potential: An Overview of Biological Aspects and Biomedical Efficacy
Current Medicinal Chemistry Chemopreventive Properties of Peptide Lunasin: A Review
Protein & Peptide Letters Evolution of Resistance to Cancer Therapy
Current Pharmaceutical Design Targeting Nodal and Cripto-1: Perspectives Inside Dual Potential Theranostic Cancer Biomarkers
Current Medicinal Chemistry Mechanisms of Corticosteroid Resistance in Severe Asthma and Chronic Obstructive Pulmonary Disease (COPD)
Current Pharmaceutical Design Retinal Ganglion Cell Gene Therapy and Visual System Repair
Current Gene Therapy Nitrogen Mustards as Anticancer Chemotherapies: Historic Perspective, Current Developments and Future Trends
Current Topics in Medicinal Chemistry Oligonucleotides as Anticancer Agents: From the Benchside to the Clinic and Beyond
Current Pharmaceutical Design Potential Interactions between miRNAs and Hypoxia: A New Layer in Cancer Hypoxia
Anti-Cancer Agents in Medicinal Chemistry Studies on Coumarins and Coumarin-Related Compounds to Determine their Therapeutic Role in the Treatment of Cancer
Current Pharmaceutical Design The Structure and Function of Histone Deacetylases: The Target for Anti-cancer Therapy
Current Medicinal Chemistry SENP1 as A Biomarker for the Diagnosis of Cancer: Review of the Science and Published Patents
Recent Patents on Biomarkers Restoration of Chemoresistance Mechanism by Novel Drug Therapies in Breast Cancer Cell Lines
Current Drug Therapy