Research Update CHF 02759 FINAL: Reprogramming the Tumor Immune Niche in Canine Hemangiosarcoma

We have made significant progress toward Objective 1 and 2 for this project. The PI, Dr. Kim has established a new laboratory for veterinary oncology research in the Department of Small Animal Clinical Sciences, at the University of Florida College of Veterinary Medicine. Over the past six months, we have successfully transferred our expertise in hemangiosarcoma research and finalized work to achieve the project objectives in the new institute. We have enhanced our knowledge of how PIK3CA gene mutations influence cellular and molecular behaviors of canine hemangiosarcoma cells.

Importantly, we have found a new way to target the gene mutations and to inhibit their functions using chemical inhibitors. In addition, we have provided high-value genomics data (ATAC-seq and single cell gene expression data) with new, updated analytic methodology. It increases genomic resolution of canine hemangiosarcoma, informing us how individual cells proliferate and survive as well as induce drug resistance. By analyzing the data, we can identify specific types of individual tumor cells among whole tumor population. Data analysis tools for cancer genomics are rapidly being developed in biotechnology field. Yet, the applications for veterinary oncology are limited. Our project provides the data resources helping veterinary research community as well as informing clinicians to improve cancer
management.

In this report, we show that PIK3CA mutations are essential for molecular change and immune regulation and the changes are detectable by conventional experimental assays as well as computational genomics analysis. The relationship between gene mutations and tumor immunity is important for canine hemangiosarcomas, because this tumor is highly inflammatory and the tumor-favorable immunity requires new, unique approaches to develop effective therapies. The results of our project will help develop additional diagnostics, especially for detection of PIK3CA mutations and new therapeutic approaches for hemangiosarcoma to improve canine health.

FINAL Update – Reprogramming the Tumor Immune Niche in Canine Hemangiosarcoma