Abstract
The enzyme poly(ADP)-ribose polymerase-1 (PARP-1) plays an important role in the repair of DNA damage via a mechanism called base excision repair (BER). Initially, inhibition of PARP-1 showed to be a promising anti-tumor strategy in preclinical models using BRCA1 and BRCA2 deficient tumor cell lines. More recently, several small molecules targeting PARP-1 entered the clinic and demonstrated compelling anti-tumor activity in patients with BRCA deficient breast and ovarian cancers, and in patients with triple-negative breast cancer. In this review we aim to summarize the most recent advances in the development of PARP inhibitors, with a focus on the clinical data.
Keywords: Synthetic lethality, repair mechanism, PARP, BRCA deficient, olaparib
Current Clinical Pharmacology
Title: Inducing Synthetic Lethality using PARP Inhibitors
Volume: 5 Issue: 3
Author(s): David S. Boss, Jos H. Beijnen and Jan H.M. Schellens
Affiliation:
Keywords: Synthetic lethality, repair mechanism, PARP, BRCA deficient, olaparib
Abstract: The enzyme poly(ADP)-ribose polymerase-1 (PARP-1) plays an important role in the repair of DNA damage via a mechanism called base excision repair (BER). Initially, inhibition of PARP-1 showed to be a promising anti-tumor strategy in preclinical models using BRCA1 and BRCA2 deficient tumor cell lines. More recently, several small molecules targeting PARP-1 entered the clinic and demonstrated compelling anti-tumor activity in patients with BRCA deficient breast and ovarian cancers, and in patients with triple-negative breast cancer. In this review we aim to summarize the most recent advances in the development of PARP inhibitors, with a focus on the clinical data.
Export Options
About this article
Cite this article as:
S. Boss David, H. Beijnen Jos and H.M. Schellens Jan, Inducing Synthetic Lethality using PARP Inhibitors, Current Clinical Pharmacology 2010; 5 (3) . https://dx.doi.org/10.2174/157488410791498798
DOI https://dx.doi.org/10.2174/157488410791498798 |
Print ISSN 1574-8847 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3938 |
Related Articles
-
TWIST1 Gene: First Insights in Felis catus
Current Genomics The Role of Mitochondria in Cancer Induction, Progression and Changes in Metabolism
Mini-Reviews in Medicinal Chemistry Estrogen Receptor Alpha: Impact of Ligands on Intracellular Shuttling and Turnover Rate in Breast Cancer Cells
Current Cancer Drug Targets Iron Chelators in Cancer Chemotherapy
Current Topics in Medicinal Chemistry Saccharomyces Cerevisiae as a Genetic Model in Anticancer Therapy
Current Pharmacogenomics Near Infrared Receptor-Targeted Nanoprobes for Early Diagnosis of Cancers
Current Medicinal Chemistry ADAMTS9-AS2: A Functional Long Non-coding RNA in Tumorigenesis
Current Pharmaceutical Design New Opportunities for Pregnane X Receptor (PXR) Targeting in Drug Development. Lessons from Enantio- and Species-Specific PXR Ligands Identified from A Discovery Library of Amino Acid Analogues
Mini-Reviews in Medicinal Chemistry Probiotics and Oral Health
Current Pharmaceutical Design Recent Advances in the Probe Development of Technetium-99m Molecular Imaging Agents
Current Organic Synthesis Fanconi Anemia Proteins, DNA Interstrand Crosslink Repair Pathways, and Cancer Therapy
Current Cancer Drug Targets Preparation and Quality Control of <sup>111</sup>In-Plerixafor for Chemokine Receptor CXCR4
Recent Patents and Topics on Imaging (Discontinued) Polyphenols Counteract Tumor Cell Chemoresistance Conferred by Multidrug Resistance Proteins
Anti-Cancer Agents in Medicinal Chemistry Natural Polymeric Nanoparticles for Brain-Targeting: Implications on Drug and Gene Delivery
Current Pharmaceutical Design Vitamin-D Receptor (VDR) Gene Polymorphisms (TaqI, FokI) in Turkish Patients with Hashimoto’s Thyroiditis: Relationship to the Levels of Vit-D and Cytokines
Endocrine, Metabolic & Immune Disorders - Drug Targets What are the Cancer Risks in BRCA Carriers Apart from Those Regarding the Breast and the Ovary?
Current Women`s Health Reviews The Psychiatric Drug Lithium Increases DNA Damage and Decreases Cell Survival in MCF-7 and MDA-MB-231 Breast Cancer Cell Lines Expos ed to Ionizing Radiation
Current Molecular Pharmacology Antineoplastic Action of Growth Hormone-Releasing Hormone (GHRH) Antagonists
Recent Patents on Anti-Cancer Drug Discovery Significance of Various Experimental Models and Assay Techniques in Cancer Diagnosis
Mini-Reviews in Medicinal Chemistry Angiogenesis as a therapeutic target in breast cancer
Mini-Reviews in Medicinal Chemistry