2011: Identification of Novel Drugs to Halt the Metastasis of Tumors That Cause Cushing's Syndrome

Grant Status: Closed

Grant Amount: $41,700
Sara Galac, DVM, PhD; University of Utrecht
January 1, 2014 - December 31, 2015

Sponsor(s): Clumber Spaniel Health Foundation, Health and Rescue Foundation of the PBGV Club of America

Breed(s): -All Dogs
Research Program Area: Endocrinology
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Abstract

Tumors of the adrenal gland that lead to Cushing's syndrome are characterized by excessive cortisol secretion which in turn causes these tumors to be aggressive and rapidly metastasize. Recently, a critical role of steroidogenic factor (SF-1) in adrenal tumor formation has been demonstrated. Elevated SF-1 levels trigger tumor formation in mice and are associated with poor prognosis in humans and dogs. Blocking SF-1 with medical compounds (SF-1 inverse agonists) may suppress both tumor growth and cortisol production, thus enhancing the ability of veterinary surgeons to successfully remove adrenocortical tumors and prevent metastasis. In this study, Dr. Galac will obtain adrenal cancer cells from dogs after adrenal surgery and culture these tumors with SF-1 inverse agonists. The effect of these SF-1 agonists on cortisol production and cell growth will be evaluated, and if drugs are found to suppress cortisol production, Dr. Galac predicts they can enter the drug pipeline for the treatment of canine adrenal cancer. Due to the similarities with adrenal cancer in humans, the results of this study could be applied to human medicine.

Publication(s)

Galac, S., Kool, M. M. J., van den Berg, M. F., Mol, J. A., & Kooistra, H. S. (2014). Expression of steroidogenic factor 1 in canine cortisol-secreting adrenocortical tumors and normal adrenals. Domestic Animal Endocrinology, 49, 1–5. https://doi.org/10.1016/j.domaniend.2014.04.002
 
Galac, Sara. (2016). Cortisol-secreting adrenocortical tumours in dogs and their relevance for human medicine. Molecular and Cellular Endocrinology, 421, 34–39. https://doi.org/10.1016/j.mce.2015.06.026
 
Galac, Sara, & Wilson, D. B. (2015). Animal Models of Adrenocortical Tumorigenesis. Endocrinology and Metabolism Clinics of North America, 44(2), 297–310. https://doi.org/10.1016/j.ecl.2015.02.003
 
Sanders, K., Mol, J. A., Kooistra, H. S., Slob, A., & Galac, S. (2016). New Insights in the Functional Zonation of the Canine Adrenal Cortex. Journal of Veterinary Internal Medicine, 30(3), 741–750. https://doi.org/10.1111/jvim.13946
 
Sanders, K., Mol, J. A., Slob, A., Kooistra, H. S., & Galac, S. (2018a). Steroidogenic factor-1 inverse agonists as a treatment option for canine hypercortisolism: In vitro study. Domestic Animal Endocrinology, 63, 23–30. https://doi.org/10.1016/j.domaniend.2017.11.001
 
Sanders, K., Mol, J. A., Slob, A., Kooistra, H. S., & Galac, S. (2018b). Steroidogenic factor-1 inverse agonists as a treatment option for canine hypercortisolism: In vitro study. Domestic Animal Endocrinology, 63, 23–30. https://doi.org/10.1016/j.domaniend.2017.11.001
 
Sanders, R. A., Kurosawa, T. A., & Sist, M. D. (2018). Ambulatory electrocardiographic evaluation of the occurrence of arrhythmias in healthy Salukis. Journal of the American Veterinary Medical Association, 252(8), 966–969. https://doi.org/10.2460/javma.252.8.966

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