03228: Identification of Tumor-Specific Proteins for Targeted Therapy in Solid and Disseminated Histiocytic Sarcoma

Grant Status: Open

Grant Amount: $92,089
Enni Markkanen, Dr. med. vet., Dr. sc. nat. and Mirja C Nolff, Dr. med. vet., DVM; University of Zurich
February 1, 2024 - January 31, 2026


Breed(s): Flat-Coated Retriever, Bernese Mountain Dog, -All Dogs
Research Program Area: Oncology
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One Health: Yes


Canine Histiocytic Sarcoma (HS) is a frequent and fatal neoplastic disease that affects dogs from different breeds, with a particular predisposition in Bernese Mountain Dogs and Flat-Coated Retrievers. As currently available therapies are unable to provide reliable and sustainable control of the disease, novel approaches are urgently needed to help affected patients. Novel approaches, such as attaching tumor-cell killing drugs to carriers that specifically bind and deliver their cargo to tumor-cells have great potential to improve care for HS patients. However, development of such approaches for HS is frustrated by a striking lack of data to identify specific structures on tumor cells that differentiate them from the normal peritumoral tissue (PTT). More detailed insight into the protein landscape of these tumors is urgently needed to enable development of better treatment modalities for HS patients.

Using an innovative approach to analyze specific areas of archival patient samples by laser-capture microdissection (LCM) and proteomics, the overarching goal of this project is to gain detailed molecular insight into the proteomic landscape of canine HS (both localized and disseminated forms) and how it differs from the healthy PTT. This will identify tumor-specific targets that can be subsequently used for development of targeted therapies. Moreover, these data will provide detailed molecular insight into the disease-driving pathways, thereby identifying novel treatment options for these underserved patients. In summary, the knowledge gained through the proposed project has tremendous potential to improve care and therapy of dogs suffering from HS. Finally, as canine HS are considered good models to better understand HS in humans, these results also have the potential to significantly impact human health from a One Health perspective.



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