Duke Researchers Find Alcohol Abuse Drug Disrupts Tumor Emboli Formation in Inflammatory Breast Cancer

Study Provides New Insights Into 3D Imaging and Targeting Tumor Emboli in Patients with Inflammatory Breast Cancer

Duke researchers have found that a drug used for alcohol abuse reduces the formation of tumor emboli in inflammatory breast cancer (IBC), one of the most lethal types of breast cancer. Current barriers to the successful treatment of IBC include the presence and frequent infiltration of tumor cell clusters, termed tumor emboli, within the breast parenchyma and lymphatics.

The finding is reported in the journal Oncotarget as a cover article along with two accompanying editorials. The study was co-led by Gayathri Devi, PhD, Division of Surgical Sciences, and Mark Dewhirst, DVM, PhD, Department of Radiation Oncology, with funding from a joint Development Award from the Duke Cancer Institute.

In the study, the research team discovered the expression of the transcription factor NFkB and the cell death regulator XIAP in the lymphatics of IBC tumors. The team developed a novel high-content, high-throughput assay to conduct a morphometric analysis of tumor emboli. This 3D assay was then used to screen for compounds that target NFkB and XIAP. The team found that the FDA-approved drug disulfiram, when combined with copper, was efficacious in targeting the formation of IBC tumor emboli.

This study included a multi-institutional collaboration with Steven Van Laere, PhD, University of Antwerp, and Kevin Williams, PhD, North Carolina State University, as part of the Duke Inflammatory Breast Cancer Consortium. This collaboration provided training in IBC research for lead author Jay Arora, an undergraduate student at Duke Trinity College of Arts and Sciences in the Dewhirst and Williams laboratories. Co-first author Scott Sauer, a postdoctoral fellow in the Devi lab, and Charlotte Rypens, a PhD student in the Van Laere’s lab, also received research training. 

The study received support from Duke Cancer Institute developmental funds awarded to Dr. Devi and Dr. Dewhirst as part of the P30 Cancer Center Support Grant NIH CA014236, the Inflammatory Breast Cancer Research Foundation and National Cancer Institute training grant T32CA009111, and Duke IBC Consortium funds from the Duke School of Medicine.

“Inflammatory breast cancer tumor emboli express high levels of anti-apoptotic proteins: use of a quantitative high content and high-throughput 3D IBC spheroid assay to identify targeting strategies”
Oncotarget. 2017; 8:25848-25863.

“Realistic modeling of tumor cells”
Oncotarget. 2017; 8:25833-25834.

“A target of potential RELAvance in inflammatory breast cancer”
Oncotarget. 2017; 8:25835-25836.