Abstract
DNA damage and genetic rearrangements are hallmarks of cancer. However, gene fusions as driver mutations in cancer have classically been a distinction in leukemia and other rare instances until recently with the discovery of gene fusion events occurring in 50 to 75% of prostate cancer patients. The discovery of the TMPRSS2-ERG fusion sparked an onslaught of discovery and innovation resulting in a delineation of prostate cancer via a molecular signature of gene fusion events. The increased commonality of high-throughput sequencing data coupled with improved bioinformatics approaches not only elucidated the molecular underpinnings of prostate cancer progression, but the mechanisms of gene fusion biogenesis. Interestingly, the androgen receptor (AR), already known to play a significant role in prostate cancer tumorigenesis, has recently been implicated in the processes resulting in gene fusions by inducing the spatial proximity of genes involved in rearrangements, promoting the formation of double-strand DNA breaks (DSB), and facilitating the recruitment of proteins for non-homologous end-joining (NHEJ). Our increased understanding of the mechanisms inducing genomic instability may lead to improved diagnostic and therapeutic strategies. To date, the majority of prostate cancer patients can be molecularly stratified based on their gene fusion status thereby increasing the potential for tailoring more specific and effective therapies.
Keywords: Androgen receptor, gene fusions, genomic instability, prostate cancer
Current Drug Targets
Title:Recurrent Rearrangements in Prostate Cancer: Causes and Therapeutic Potential
Volume: 14 Issue: 4
Author(s): Nicole M. White, Felix Y. Feng and Christopher A. Maher
Affiliation:
Keywords: Androgen receptor, gene fusions, genomic instability, prostate cancer
Abstract: DNA damage and genetic rearrangements are hallmarks of cancer. However, gene fusions as driver mutations in cancer have classically been a distinction in leukemia and other rare instances until recently with the discovery of gene fusion events occurring in 50 to 75% of prostate cancer patients. The discovery of the TMPRSS2-ERG fusion sparked an onslaught of discovery and innovation resulting in a delineation of prostate cancer via a molecular signature of gene fusion events. The increased commonality of high-throughput sequencing data coupled with improved bioinformatics approaches not only elucidated the molecular underpinnings of prostate cancer progression, but the mechanisms of gene fusion biogenesis. Interestingly, the androgen receptor (AR), already known to play a significant role in prostate cancer tumorigenesis, has recently been implicated in the processes resulting in gene fusions by inducing the spatial proximity of genes involved in rearrangements, promoting the formation of double-strand DNA breaks (DSB), and facilitating the recruitment of proteins for non-homologous end-joining (NHEJ). Our increased understanding of the mechanisms inducing genomic instability may lead to improved diagnostic and therapeutic strategies. To date, the majority of prostate cancer patients can be molecularly stratified based on their gene fusion status thereby increasing the potential for tailoring more specific and effective therapies.
Export Options
About this article
Cite this article as:
M. White Nicole, Y. Feng Felix and A. Maher Christopher, Recurrent Rearrangements in Prostate Cancer: Causes and Therapeutic Potential, Current Drug Targets 2013; 14 (4) . https://dx.doi.org/10.2174/1389450111314040006
DOI https://dx.doi.org/10.2174/1389450111314040006 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
Therapeutic Chemical and RNA Design with Artificial Intelligence
Computer-Aided Drug Design (CADD) has emerged as a fundamental component of modern drug discovery. Molecular docking facilitates virtual screening on a large scale through structural simulations. However, traditional CADD approaches face significant limitations, as they can only screen known compounds from existing libraries. PubChem, as the most widely used chemical ...read more

- 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
Related Articles
-
TRAIL Gene Therapy: From Preclinical Development to Clinical Application
Current Gene Therapy Progress in Immunotherapy of Head and Neck Squamous Cell Carcinoma
Current Molecular Pharmacology Targeting Blood Vessels for the Treatment of Non-Small Cell Lung Cancer
Current Cancer Drug Targets Current Challenges in Targeting Tumor Desmoplasia to Improve the Efficacy of Immunotherapy
Current Cancer Drug Targets Design, Synthesis, and Biological Evaluation of C-2 Substituted 3Hthieno[ 2,3-d]pyrimidin-4-one Derivatives as Novel FGFR1 Inhibitors
Medicinal Chemistry Gene Expression Profiles in Breast Cancer to Identify Estrogen Receptor Target Genes
Mini-Reviews in Medicinal Chemistry Discovery and Applications of Disulfide-Rich Cyclic Peptides
Current Topics in Medicinal Chemistry Hyperpolarized 13Carbon MR
Current Pharmaceutical Biotechnology Cytotoxic Compounds in the Treatment of Castration-Resistant Prostate Cancer
Anti-Cancer Agents in Medicinal Chemistry Hypoxic Radiosensitizers and Hypoxic Cytotoxins in Radiation Oncology
Current Medicinal Chemistry - Anti-Cancer Agents Efflux Pump Inhibitors: A Novel Approach to Combat Efflux-Mediated Drug Resistance in Bacteria
Current Drug Targets RO3280: A Novel PLK1 Inhibitor, Suppressed the Proliferation of MCF-7 Breast Cancer Cells Through the Induction of Cell Cycle Arrest at G2/M Point
Anti-Cancer Agents in Medicinal Chemistry Glioma: Tryptophan Catabolite and Melatoninergic Pathways Link microRNA, 14-3- 3, Chromosome 4q35, Epigenetic Processes and other Glioma Biochemical Changes
Current Pharmaceutical Design Adiponectin as a Potential Therapeutic Target for Prostate Cancer
Current Pharmaceutical Design Oncoproteomics of Neuroblastoma: A Blueprint for Future Progress
Current Proteomics Biomimetic Approaches for Targeted Nanomedicine: Current Status and Future Perspectives
Current Drug Therapy Glutathione Transferases as Targets for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Fragment-Based Optimization of Small Molecule CXCL12 Inhibitors for Antagonizing the CXCL12/CXCR4 Interaction
Current Topics in Medicinal Chemistry Imaging Methods in Gene Therapy of Cancer
Current Gene Therapy Dendrimer-drug Conjugates in Drug Delivery and Targeting
Pharmaceutical Nanotechnology