Identification of Novel Agents for the Treatment of Brain Metastases of Breast Cancer

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.

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