鉴定用于治疗乳腺癌脑转移瘤的新药

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

Volume: 17 Issue: 5

关键词: 耐药性，CNS，分布，脑癌，药物发现，化疗，ADME。

摘要: 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:

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