03017: Molecular Characterization of Canine Soft Tissue Sarcomas Using Spatially Defined Proteomics and Transcriptomics

One Health: Yes

Abstract

Soft-tissue sarcomas (STS) are frequent cancers that affect dogs of all breeds and can occur almost anywhere in the body. Therapy usually consists of surgical removal of these tumors, but it is difficult for the surgeon to distinguish the exact borders of the tumor, which often leads to incomplete removal and regrowth of the tumor in many affected patients. Novel approaches, such as specific anticancer drugs or tumor-cell-specific dyes to improve visualization during surgery have great potential to improve care for STS patients. However, the development of such approaches for STS is frustrated by a striking lack of molecular data to illuminate what mechanisms drive the growth of these tumors or to define targets that specifically differentiate tumor cells from the normal peritumoral tissue (PTT). This lack of knowledge on an extremely relevant canine tumor type warrants further investigation.

Using an innovative approach to analyze specific areas of archival patient samples by laser-capture microdissection (LCM), RNAsequencing, and proteomics, the overarching goal of this project is to gain a detailed molecular understanding of the very frequent STS subtypes: perivascular wall tumors (PWT) and peripheral nerve sheath tumors (PNST). This information will complement preliminary data for fibrosarcoma (FSA) and may enable development of future novel diagnostic and therapeutic modalities for patients, including identification of specific anticancer drugs and targeted tumor visualization strategies to guide surgical excision of STS. As complete tumor removal with clean margins is the most important factor to influence recurrence, metastasis, and survival in patients, precise visualization of STS has tremendous potential to improve the currently available options to treat these canine cancers. The knowledge gained through the study will work to improve the care and therapy of dogs with STS. Additionally, as canine STS are considered good models to better understand STS in humans, these results also have the potential to significantly impact human health from a One Health perspective.

Publication(s)

Beebe E, Pöschel A, Kunz L, Wolski W, Motamed Z, Meier D, Guscetti F, Nolff MC and Markkanen E: Proteomic profiling of canine fibrosarcoma and adjacent peritumoral tissue. Neoplasia 2023. doi: 10.1016/j.neo.2022.100858