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
-
Natural Products as Aromatase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Estrogenic Phenol and Catechol Metabolites of PCBs Modulate Catechol-Omethyltransferase Expression Via the Estrogen Receptor: Potential Contribution to Cancer Risk
Current Drug Metabolism Antioxidant Properties of Melatonin and its Potential Action in Diseases
Current Topics in Medicinal Chemistry Dual Induction of Mitochondrial Apoptosis and Senescence in Chronic Myelogenous Leukemia by Myrtucommulone A
Anti-Cancer Agents in Medicinal Chemistry Patent Selections:
Recent Patents on Inflammation & Allergy Drug Discovery Oxidative Phosphorylation as a Target to Arrest Malignant Neoplasias
Current Medicinal Chemistry Adipose Tissue: Something More than Just Adipocytes
Current Nutrition & Food Science Big Data to Knowledge: Application of Machine Learning to Predictive Modeling of Therapeutic Response in Cancer
Current Genomics Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention: A Case-control Study
Current Nutrition & Food Science The Importance of Stereochemistry on the Actions of Vitamin D
Current Topics in Medicinal Chemistry Autophagy Regulators as Potential Cancer Therapeutic agents: A Review
Current Topics in Medicinal Chemistry Alpha-Terpineol as Antitumor Candidate in Pre-Clinical Studies
Anti-Cancer Agents in Medicinal Chemistry Biomimetic Approaches Towards The Synthesis of Complex Dimeric Natural Products
Current Pharmaceutical Design MicroRNAs: Association with Radioresistant and Potential Uses of Natural Remedies as Green Gene Therapeutic Approaches
Current Gene Therapy NF-κ B and Rheumatic Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Patent Selections
Recent Patents on Biomarkers Editorial (Thematic Issue: Recent Developments in the Chemistry of Anti-Cancer Drug Research)
Current Organic Chemistry Infrared-Spectroscopy: A Non-Invasive Tool for Medical Diagnostics and Drug Analysis
Current Medicinal Chemistry Evaluation of a New <sup>99m</sup>Tc-labeled GnRH Analogue as a Possible Imaging Agent for Prostate Cancer Detection
Anti-Cancer Agents in Medicinal Chemistry Mitophagy in Carcinogenesis and Tumour Progression- A New Paradigm with Emerging Importance
Anti-Cancer Agents in Medicinal Chemistry