Evaluating the Radiosensitivities of Chemo-Radiation Treatments for Brain Metastatic Breast Cancer.

William Pentz*, Samuel Sprowls, Vincenzo Pizzuti, Tasneem Arsiwala and Paul Lockman, Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506

Field (Broad Category): Pharmaceutical Sciences (Health Sciences) 

Student’s Major: Biochemistry and Mathematics 

Hindrance of drug passage across the blood-brain barrier (BBB) limits the efficacy of current chemoradiation therapy treatments for brain metastatic tumors. However, over the past decade, improved targeted-drug delivery methods and novel temporary BBB disruption mechanisms are beginning to make localized administration of chemotherapeutics into brain lesions a viable option. Currently, literature evaluating the radiosensitizing effects of chemotherapeutics on brain metastatic cell lines is limited. This study evaluates the radiosensitizing effects of doxorubicin on the brain metastatic breast cancer cell line MDA-MB-231-Br. MTT assays were used to predict necessary doxorubicin concentrations for a 24-hour incubation period after irradiation. In vitro radiosensitivity was assessed with clonogenic assays. The linearquadratic model was used to provide quantitative values to the radiosensitivities of the cell line with and without doxorubicin. Between 0-9 Gy, 15nM doxorubicin had a predicted sensitizer-enhancement ratio of 1.51. Due to the dynamic environment and heterogeneous characteristics of metastatic cancers seen in vivo, performing concurrent chemotherapy and radiation therapy treatments in a controlled in vitro environment provides a fundamental basis for evaluating the inherent interactions between the two modalities. 

Funding: Mylan Chair Endowment 

Program/mechanism supporting research/creative efforts: Capstone Course within Department AGBI 486: UG Research Experience 2