Identifying Cancer Inhibitory Drugs that Can Penetrate the Blood-Brain Barrier

Rachel Gadd*, Sam Sprowls, Lealand Earp and Paul Lockman, Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506

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

Student’s Major: Biochemistry 

Breast cancer (BC) affects a large proportion of women every year. The most severe complication of BC occurs when a primary tumor cell moves from the breast to the brain creating a brain metastatic tumor. Some palliative options include chemotherapy, radiotherapy, and/or surgical removal if the patient is medically operable. However, radiation and surgery are rarely curative, and an overwhelming majority of chemotherapies are rendered ineffective because the therapeutics cannot penetrate the blood-brain barrier (BBB). Thus, different agents are needed that can penetrate the BBB and successfully treat BC brain lesions. To find new anti-cancer agents, high through-put screens will be used to identify candidates with anti-cancer activity from a panel of investigatory compounds. Once candidates are identified a half maximal inhibitory concentration (IC50) assay will be conducted with different hits to determine what concentration of the candidate is necessary to kill half of the total cancer cells present. Hits are defined as agents that successfully kill cancer cells as discovered through the IC50 experiments. These medications will be used to treat mice with breast cancer to access how well these medications perform in live specimens. Hopefully, a breast cancer inhibitory drug can be identified from this experiment and used to successfully treat cancer in mice. Once this is accomplished the new drug can go on to be tested in clinical trials and hopefully successfully treat breast cancer patients with brain metastases. 

Funding: NIGMS:P20GM121322 and the Mylan Chair Endowment Fund 

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course