02321: Clinical Trial of Procaspase-3 Activator (PAC-1) in Combination with Hydroxyurea for Treatment of Canine Meningioma

Grant Status: Closed

Grant Amount: $51,191
Timothy M. Fan, DVM, PhD; University of Illinois
February 1, 2017 - January 31, 2021

Sponsor(s): American Boxer Charitable Foundation

Breed(s): -All Dogs
Research Program Area: Oncology
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One Health: Yes


Primary brain tumors are a significant cause of illness and death in pet dogs, with meningioma accounting for approximately half of the cases seen by veterinary neurologists and oncologists. Although surgery remains the best treatment for dogs with meningioma, some dogs are not good candidates for this approach based on their tumor size and/or location. Dogs also may experience tumor regrowth after an attempt is made to surgically remove the tumor. In these situations, effective treatment options are limited. Thus, new treatments that are both safe and effective are needed for dogs with meningioma. A team of investigators from the National Cancer Institute's Comparative Oncology Program (NCI-COP) and selected veterinary academic centers will work together using state-of-the art imaging and a novel therapeutic approach for dogs with meningioma that are good surgical candidates. Dogs enrolled in this study will receive an investigational combination of chemotherapy agents (PAC-1 + hydroxyurea) and will be monitored with magnetic resonance and non-invasive molecular imaging techniques. Dogs will then undergo tumor removal and tissue analysis. This approach is the first to validate and advance a new therapy that is directly applicable to dogs, and potentially also to humans, with advanced, locally-recurrent, and/or non-resectable meningioma.


Tonogai, E. J., Huang, S., Botham, R. C., Berry, M. R., Joslyn, S. K., Daniel, G. B., Chen, Z., Rao, J., Zhang, X., Basuli, F., Rossmeisl, J. H., Riggins, G. J., LeBlanc, A. K., Fan, T. M., & Hergenrother, P. J. (2021). Evaluation of a procaspase-3 activator with hydroxyurea or temozolomide against high-grade meningioma in cell culture and canine cancer patients. Neuro-Oncology, noab161. https://doi.org/10.1093/neuonc/noab161

Schlein, L. J., Fadl-Alla, B., Pondenis, H. C., Lezmi, S., Eberhart, C. G., LeBlanc, A. K., … Fan, T. M. (2019). Immunohistochemical Characterization of Procaspase-3 Overexpression as a Druggable Target With PAC-1, a Procaspase-3 Activator, in Canine and Human Brain Cancers. Frontiers in Oncology, 9 (96). https://doi.org/10.3389/fonc.2019.00096

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