One of two prestigious 2016 WARF Discovery Challenge grants was awarded to Brynna Wilken-Resman, NSF predoctoral fellow, in the laboratory of Robert Thorne, assistant professor in drug delivery in the Pharmaceutical Sciences Division, and Dmitry Malin, PhD, from the laboratory of Vincent Cryns, MD, Chief, Division of Endocrinology, Diabetes and Metabolism, and Marian A. and Rodney P. Burgenske Chair, UW Madison School of Medicine and Public Health.

The highly novel collaboration between Wilken-Resman and Malin is for new research that aims to shed light on a major roadblock to the use of antibodies for the treatment of breast cancer brain metastases and the current lack of knowledge regarding how antibodies distribute through the brain after intrathecal delivery.

The Cryns lab has recently developed orthotopic models of breast cancer brain metastasis using fluorescently labeled cancer cells that metastasize from the mammary gland to the brain. These innovative mouse models recapitulate breast cancer brain metastasis in patients because they utilize triple negative breast cancer (TNBC) cells, which commonly metastasize to the brain.

The Thorne lab employs state-of-the-art in vivo imaging methodology and has recently has developed new methods for ex vivo fluorescence imaging and high resolution confocal imaging of the brain and spinal cord following central administration of antibodies and other macromolecules. The proposed studies are highly interdisciplinary, coupling the neuroscience/pharmaceutical sciences/bioengineering expertise of the Thorne group with the cancer biology/clinical oncology expertise of the Cryns group. The Thorne lab has extensive knowledge of the Central Nervous System (CNS) and its complex environment, extensive experience with intrathecal administration, and well-developed image analysis techniques.

The funded project will be a joint effort between the Thorne and Cryns laboratory and is expected to yield critical guidance and new information on the treatment of brain metastases, a devastating complication in 10-16% of women with breast cancer and for whom overall median survival is seven months.

Robert Thorne’s research interests include mechanisms and strategies for the central nervous system delivery and distribution of biologics (peptides, proteins, siRNA, nanoparticles, and viral gene therapy vectors). With further focus on antibody-based drugs and adeno-associated virus vectors for gene therapy; intraparenchymal, intrathecal and intranasal routes of administration.

The Cryns lab focuses on understanding how tumors adapt to and survive metabolic stress caused by their rapid growth. These metabolic adaptions are unique to cancer cells and represent promising drug targets to selectively eradicate tumors. They are particularly interested in translating these insights into improved cancer biomarkers and therapies.