Abstract
Prostate cancer is the most frequently diagnosed tumor in industrialized countries. Endocrine therapy, which is based on interference with androgen signaling is only palliative. Drugs used in prostate cancer therapy are luteinizing hormone releasing hormone (LHRH) agonists and antiandrogens. Application of LHRH agonists leads to suppression of the levels of circulating androgens, and antiandrogens block the function of the androgen receptor (AR). The steroidal antiandrogen cyproterone acetate and nonsteroidal compounds hydroxyflutamide and bicalutamide are used most frequently. They prevent acquisition of a transcriptionally active conformation of the AR. It became clear that tumors progress to therapy resistance in the presence of the AR which might be structurally altered. These mutations generate receptors that respond to other steroids and antiandrogens by increased activation. In addition, AR expression increases during endocrine treatment. AR is also activated by nonsteroidal compounds such as growth factors, interleukin-6, and neuropeptides. Therefore, new experimental approaches are needed to antagonize AR expression and function more efficiently. The AR associates with a number of proteins, coactivators and corepressors. There are indications that expression of some of these proteins is altered in prostate cancer, a fact which might be important for improvement of endocrine therapy.
Keywords: Antiandrogens, luteinizing hormone releasing hormone (LHRH), nonsteroidal, corepressors, proteins
Current Cancer Drug Targets
Title: Antiandrogens in Prostate Cancer Endocrine Therapy
Volume: 4 Issue: 5
Author(s): Z. Culig, G. Bartsch and A. Bartsch
Affiliation:
Keywords: Antiandrogens, luteinizing hormone releasing hormone (LHRH), nonsteroidal, corepressors, proteins
Abstract: Prostate cancer is the most frequently diagnosed tumor in industrialized countries. Endocrine therapy, which is based on interference with androgen signaling is only palliative. Drugs used in prostate cancer therapy are luteinizing hormone releasing hormone (LHRH) agonists and antiandrogens. Application of LHRH agonists leads to suppression of the levels of circulating androgens, and antiandrogens block the function of the androgen receptor (AR). The steroidal antiandrogen cyproterone acetate and nonsteroidal compounds hydroxyflutamide and bicalutamide are used most frequently. They prevent acquisition of a transcriptionally active conformation of the AR. It became clear that tumors progress to therapy resistance in the presence of the AR which might be structurally altered. These mutations generate receptors that respond to other steroids and antiandrogens by increased activation. In addition, AR expression increases during endocrine treatment. AR is also activated by nonsteroidal compounds such as growth factors, interleukin-6, and neuropeptides. Therefore, new experimental approaches are needed to antagonize AR expression and function more efficiently. The AR associates with a number of proteins, coactivators and corepressors. There are indications that expression of some of these proteins is altered in prostate cancer, a fact which might be important for improvement of endocrine therapy.
Export Options
About this article
Cite this article as:
Culig Z., Bartsch G. and Bartsch A., Antiandrogens in Prostate Cancer Endocrine Therapy, Current Cancer Drug Targets 2004; 4 (5) . https://dx.doi.org/10.2174/1568009043332925
DOI https://dx.doi.org/10.2174/1568009043332925 |
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
-
Recent Developments on 1,2,4-Triazole Nucleus in Anticancer Compounds: A Review
Anti-Cancer Agents in Medicinal Chemistry Flavonoids as Multi-Target Compounds in Drug Discovery
Mini-Reviews in Organic Chemistry Spirooxindoles as Potential Pharmacophores
Mini-Reviews in Medicinal Chemistry Disease-Related Changes in TRPV1 Expression and Its Implications for Drug Development
Current Topics in Medicinal Chemistry An Update on Circumventing Multidrug Resistance in Cancer by Targeting P-Glycoprotein
Current Cancer Drug Targets Applications of Nanosystems to Anticancer Drug Therapy (Part II. Dendrimers, Micelles, Lipid-based Nanosystems)
Recent Patents on Anti-Cancer Drug Discovery Hotspot Mutations in DICER1 Causing GLOW Syndrome-Associated Macrocephaly <i>via</i> Modulation of Specific microRNA Populations Result in the Activation of PI3K/ATK/mTOR Signaling
MicroRNA The Multifaceted Roles of Osteopontin in Cell Signaling, Tumor Progression and Angiogenesis
Current Molecular Medicine Herbal Medicine of the 21st Century: A Focus on the Chemistry, Pharmacokinetics and Toxicity of Five Widely Advocated Phytotherapies
Current Topics in Medicinal Chemistry Synergy of microRNA and Stem Cell: A Novel Therapeutic Approach for Diabetes Mellitus and Cardiovascular Diseases
Current Diabetes Reviews New Molecular Targets of Anticancer Therapy – Current Status and Perspectives
Current Medicinal Chemistry Metabolomic Heterogeneity of Urogenital Tract Cancers Analyzed by Complementary Chromatographic Techniques Coupled with Mass Spectrometry
Current Medicinal Chemistry MicroRNA-183 Functions As an Oncogene by Regulating PDCD4 in Gastric Cancer
Anti-Cancer Agents in Medicinal Chemistry Influence of Aldo-keto Reductase 1C3 in Prostate Cancer - A Mini Review
Current Cancer Drug Targets Probing Gallic Acid for Its Broad Spectrum Applications
Mini-Reviews in Medicinal Chemistry Editorial [Hot Topic: Adrenergic Receptors as Novel Targets for Cancer Therapy (Guest Editors: D.G. Powe and F. Entschladen)]
Current Cancer Therapy Reviews Approaches to Improve Efficiency of Dendritic Cell-based Therapy of High Grade Gliomas
Current Pharmaceutical Design “Antisurvival” Factor Treatment for Hormone Refractory Prostate Cancer: Secondary Hormonal Ablation Using Somatostatin Analogs
Current Cancer Therapy Reviews The Antioxidants and Pro-Antioxidants Network: An Overview
Current Pharmaceutical Design Plasticity of Neuroendocrine-Immune Interactions During Ontogeny: Role of Perinatal Programming in Pathogenesis of Inflammation and Stress- Related Diseases in Adults
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery