Abstract
The prognosis of malignant glioma and metastatic brain tumours is still extremely poor, despite recent advances in therapeutic strategies with molecular-targeted agents. Poly(ADP-ribose) polymerase (PARP) inhibitors are a promising, novel class of anticancer drugs to be used either as single agents or in combination with chemotherapy and radiotherapy. PARP-1 and PARP-2 are the only PARP proteins that bind to DNA single strand breaks (SSBs), facilitating the repair process by the base excision repair. For this reason, PARPs have been extensively investigated as targets of novel drugs that may be used to enhance the antitumour activity of SSBs inducing agents, such as the methylating compound temozolomide, which is the drug of choice for glioblastoma, or ionizing radiations. Moreover, PARP inhibitors exert cytotoxic effects in monotherapy in BRCA mutated tumours, which are defective in the homologous recombination (HR) repair. Finally, recent studies have shown that inhibition of PARP function might also induce anti-angiogenic effects which might contribute to impair tumour growth.
Many clinical trials with PARP inhibitors are ongoing for the treatment of a variety of advanced solid tumours, including primary or secondary brain tumours. This review discusses the implications of targeting PARP on the design of new treatment regimens.
Keywords: Angiogenesis, chemoresistance, combination therapy, molecular-targeted therapy, poly(ADP-ribose) polymerase (PARP) inhibitors, telomere, temozolomide, topoisomerase I inhibitors, 6-Thioguanine, Base Excision Repair, DNA-dependent Protein Kinase, Homologous Recombination, Non Homologous DNA End Joining, Phosphate and Tension Homolog, Platelet-derived Growth Factor Receptor
Current Cancer Drug Targets
Title: Targeted Therapy for Brain Tumours: Role of PARP Inhibitors
Volume: 12 Issue: 3
Author(s): C. Leonetti, A. Biroccio, G. Graziani and L. Tentori
Affiliation:
Keywords: Angiogenesis, chemoresistance, combination therapy, molecular-targeted therapy, poly(ADP-ribose) polymerase (PARP) inhibitors, telomere, temozolomide, topoisomerase I inhibitors, 6-Thioguanine, Base Excision Repair, DNA-dependent Protein Kinase, Homologous Recombination, Non Homologous DNA End Joining, Phosphate and Tension Homolog, Platelet-derived Growth Factor Receptor
Abstract: The prognosis of malignant glioma and metastatic brain tumours is still extremely poor, despite recent advances in therapeutic strategies with molecular-targeted agents. Poly(ADP-ribose) polymerase (PARP) inhibitors are a promising, novel class of anticancer drugs to be used either as single agents or in combination with chemotherapy and radiotherapy. PARP-1 and PARP-2 are the only PARP proteins that bind to DNA single strand breaks (SSBs), facilitating the repair process by the base excision repair. For this reason, PARPs have been extensively investigated as targets of novel drugs that may be used to enhance the antitumour activity of SSBs inducing agents, such as the methylating compound temozolomide, which is the drug of choice for glioblastoma, or ionizing radiations. Moreover, PARP inhibitors exert cytotoxic effects in monotherapy in BRCA mutated tumours, which are defective in the homologous recombination (HR) repair. Finally, recent studies have shown that inhibition of PARP function might also induce anti-angiogenic effects which might contribute to impair tumour growth.
Many clinical trials with PARP inhibitors are ongoing for the treatment of a variety of advanced solid tumours, including primary or secondary brain tumours. This review discusses the implications of targeting PARP on the design of new treatment regimens.
Export Options
About this article
Cite this article as:
Leonetti C., Biroccio A., Graziani G. and Tentori L., Targeted Therapy for Brain Tumours: Role of PARP Inhibitors, Current Cancer Drug Targets 2012; 12 (3) . https://dx.doi.org/10.2174/156800912799277403
DOI https://dx.doi.org/10.2174/156800912799277403 |
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
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...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
- 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
-
Nitrones: A Potential New Alternative as Therapeutic Agents
Current Organic Chemistry T2/FLAIR Hyperintensity in Mesial Temporal Lobe: Challenging Differential Diagnosis
Current Medical Imaging Pancreatic Cancer: Systemic Combination Therapies for a Heterogeneous Disease
Current Pharmaceutical Design A Fatal Case of Acute Interstitial Pneumonia (AIP) in a Woman Affected by Glioblastoma
Current Drug Safety Exploring the Role of Phytochemicals as Potent Natural Photosensitizers in Photodynamic Therapy
Anti-Cancer Agents in Medicinal Chemistry Meet Our Editorial Board Member
Current Drug Delivery Glycogen Metabolism and Brain Pathologies
Central Nervous System Agents in Medicinal Chemistry Recent Trends of Chalcones Potentialities as Antiproliferative and Antiresistance Agents
Anti-Cancer Agents in Medicinal Chemistry The Effectiveness of Nanoparticles on Gene Therapy for Glioblastoma Cells Apoptosis: A Systematic Review
Current Gene Therapy Anticancer Advances of Matrine and Its Derivatives
Current Pharmaceutical Design Impact of Drug Metabolism/Pharmacokinetics and their Relevance Upon Taxus-based Drug Development
Current Drug Metabolism Ubiquitin-Protein Ligases - Novel Therapeutic Targets?
Current Protein & Peptide Science Notch-Associated MicroRNAs in Cancer
Current Drug Targets Targeting Invasion Induction as a Therapeutic Strategy for the Treatment of Cancer
Current Cancer Drug Targets PRL-3, An Emerging Marker of Carcinogenesis, Is Strongly Associated with Poor Prognosis
Anti-Cancer Agents in Medicinal Chemistry Radiogenetic Therapy: Strategies to Overcome Tumor Resistance
Current Pharmaceutical Design Targeting Prostate Cancer Stem Cells
Anti-Cancer Agents in Medicinal Chemistry The Use of Anthracyclines for Therapy of CNS Tumors
Anti-Cancer Agents in Medicinal Chemistry Analysis of Microarray Gene Expression Data
Current Bioinformatics Hypoxia Inducible Factor-1 as a Target for Neurodegenerative Diseases
Current Medicinal Chemistry