Abstract
Background: Brain cancer from metastasized breast cancer has a high mortality rate in women. The treatment of lesions is hampered in large part by the blood-brain barrier (BBB), which prevents adequate distribution of anti-cancer compounds to brain metastases.
Method: In this study we used a novel screening method to identify candidate molecules that are well-suited to utilizing the BBB choline transporter for distribution into the brain parenchyma. Results: From our screen we identified two compounds, Ch-1 and Ch-2 that were able to reduce the brain tumor burden in a murine mouse model of brain metastasis of breast cancer. These compounds also significantly increased the survival of mice by more than 10 days. Mechanistic studies indicated that Ch-1 is able to prevent the activation of the pro-survival mitogen-activated kinases (MAPKs) by osteoactivin (OA; Glycoprotein nonmetastatic melanoma protein B GPNMB). Conclusion: The results from this study show that nutrient transporter virtual screening is a viable novel alternative to traditional drug screening programs to identify anti-cancer compounds for the treatment of brain cancers.Keywords: Drug resistance, CNS, distribution, brain cancer, drug discovery, chemotherapy, ADME.
Current Cancer Drug Targets
Title:Identification of Novel Agents for the Treatment of Brain Metastases of Breast Cancer
Volume: 17 Issue: 5
Author(s): Vinay K. Venishetty, Werner J. Geldenhuys, Tori B. Terell-Hall, Jessica I.G. Griffith, Gregory R. Sondag, Fayez F. Safadi and Paul R. Lockman*
Affiliation:
- Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV,United States
Keywords: Drug resistance, CNS, distribution, brain cancer, drug discovery, chemotherapy, ADME.
Abstract: Background: Brain cancer from metastasized breast cancer has a high mortality rate in women. The treatment of lesions is hampered in large part by the blood-brain barrier (BBB), which prevents adequate distribution of anti-cancer compounds to brain metastases.
Method: In this study we used a novel screening method to identify candidate molecules that are well-suited to utilizing the BBB choline transporter for distribution into the brain parenchyma. Results: From our screen we identified two compounds, Ch-1 and Ch-2 that were able to reduce the brain tumor burden in a murine mouse model of brain metastasis of breast cancer. These compounds also significantly increased the survival of mice by more than 10 days. Mechanistic studies indicated that Ch-1 is able to prevent the activation of the pro-survival mitogen-activated kinases (MAPKs) by osteoactivin (OA; Glycoprotein nonmetastatic melanoma protein B GPNMB). Conclusion: The results from this study show that nutrient transporter virtual screening is a viable novel alternative to traditional drug screening programs to identify anti-cancer compounds for the treatment of brain cancers.Export Options
About this article
Cite this article as:
Venishetty K. Vinay, Geldenhuys J. Werner, Terell-Hall B. Tori, Griffith I.G. Jessica, Sondag R. Gregory, Safadi F. Fayez and Lockman R. Paul*, Identification of Novel Agents for the Treatment of Brain Metastases of Breast Cancer, Current Cancer Drug Targets 2017; 17 (5) . https://dx.doi.org/10.2174/1568009617666161121123948
DOI https://dx.doi.org/10.2174/1568009617666161121123948 |
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
-
A Transporter Gene (Sodium Iodide Symporter) for Dual Purposes in Gene Therapy: Imaging and Therapy
Current Gene Therapy Targeted Delivery of Anti-Inflammatory Agents to Tumors
Current Pharmaceutical Design Apoptosis-Induction is A Novel Therapeutic Strategy for Gastrointestinal and Liver Cancers
Current Gene Therapy Clinical Molecular Imaging with PET Agents Other than 18F-FDG
Current Pharmaceutical Biotechnology TNFα Modulation of Visceral and Spinal Sensory Processing
Current Pharmaceutical Design Quantifying Gene Co-Expression Heterogeneity in Cancer Towards Efficient Network Biomarker Design
Current Bioinformatics Development of Radicicol Analogues
Current Cancer Drug Targets Biogenic Silver and Zero-Valent Iron Nanoparticles by Feijoa: Biosynthesis, Characterization, Cytotoxic, Antibacterial and Antioxidant Activities
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in the Medicinal Chemistry of α-Aminoboronic Acids, Amine-Carboxyboranes and Their Derivatives
Mini-Reviews in Medicinal Chemistry Thymidine Phosphorylase and Fluoropyrimidines Efficacy: A Jekyl and Hyde Story
Current Medicinal Chemistry - Anti-Cancer Agents Applications of Nanosystems to Anticancer Drug Therapy (Part II. Dendrimers, Micelles, Lipid-based Nanosystems)
Recent Patents on Anti-Cancer Drug Discovery Pharmacokinetic Analysis of Taxane Through a Validated Ultra-High Performance Liquid Chromatography-Synapt Mass Spectrometry (UHPLC-MS/MS ESI-Q-TOF) Method
Current Bioactive Compounds The Anticancer Properties of Dietary Polyphenols and its Relation with Apoptosis
Current Pharmaceutical Design Meet Our Editorial Board Member
Recent Patents on Anti-Cancer Drug Discovery Mechanisms of Neuronal Damage and Neuroprotection Underlying Ischemia/Reperfusion Injury after Physical Exercise
Current Drug Targets AKT: A Potential Target for Thyroid Cancer Therapy
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Nanocarriers for the Simultaneous Co-Delivery of Therapeutic Genes and Anticancer Drugs
Current Pharmaceutical Biotechnology Molecular Imaging in Optical Coherence Tomography
Current Molecular Imaging (Discontinued) The Role of Chinese Herbs and Acupuncture on the Inflammation Reaction After Cerebral Ischemia
Current Pharmaceutical Design Mechanism of Action of Limonene in Tumor Cells: A Systematic Review and Meta-Analysis
Current Pharmaceutical Design