# Advancing precision medicine through development of the canine comparative cancer model

> **NIH NIH F32** · BROAD INSTITUTE, INC. · 2021 · $68,094

## Abstract

Project Abstract
Background: Angiosarcoma is a rare and aggressive cancer for which new treatments are urgently needed.
Efforts to implement precision medicine in this cancer are hindered by its rarity, disease heterogeneity, the time
needed to collect informative clinical data, and the emergence of chemotherapeutic resistance. Liquid biopsy is
a promising new technique allowing the sequencing of tumor DNA circulating in the plasma as a proxy for
tumor biopsy. This noninvasive technique has great potential to improve patient outcomes by allowing for
longitudinal monitoring. However, in order for this technique to be applied in the clinic, key questions regarding
its optimal use must be answered. I propose to develop liquid biopsy as a clinical monitoring strategy in
angiosarcoma using the pet dog as a model. ​Dogs commonly develop hemangiosarcoma, which is highly
similar to angiosarcoma at the clinical, histopathological, and genomic level. The dog model thus offers the
opportunity to implement rapid clinical trials for a rare cancer in a large patient population​.
Objective/Hypothesis: ​I propose to advance the use of liquid biopsy as a viable clinical strategy to
monitor treatment response, and to identify relapse earlier, by harnessing the strengths of the canine
angiosarcoma model. Furthermore, I will address a major cause of patient mortality by characterizing
mechanisms of doxorubicin resistance. Specific Aims: ​(Aim 1) I will validate canine hemangiosarcoma as
a model for human angiosarcoma at the genomic level through detailed characterization of somatic mutations
in whole-genome and whole-exome sequencing. (Aim 2) I will optimize protocols for liquid biopsy in a cohort of
canine hemangiosarcoma patients in order to maximize the diagnostic quality of the samples, and implement
and refine techniques for tracking minimal residual disease (MRD). (Aim 3) I will identify mutations associated
with doxorubicin resistance. Resistance leading to disease progression is a major cause of patient mortality,
and I will determine whether these mechanisms can be targeted using existing therapeutics. ​Study Design:
Thirty dogs with splenic hemangiosarcoma will be enrolled prospectively at diagnosis. Tumor and normal
samples will be collected at surgery, and longitudinal blood samples drawn at diagnosis, surgery, and at each
doxorubicin treatment until relapse. (Aim 1) I will perform tumor/normal whole genome sequencing of a subset
of cases, which will allow for characterization of regulatory and structural variants, and will compare these
results to the whole exome data currently being generated by The Angiosarcoma Project. (Aim 2) I will develop
and refine methods for sampling cfDNA for longitudinal monitoring of MRD, through testing of different
phlebotomy protocols, and designing patient-specific hybrid capture probes. (Aim 3) ​I will identify mutations
associated with doxorubicin resistance, by analyzing somatic mutations in the same patient at diagno...

## Key facts

- **NIH application ID:** 10077203
- **Project number:** 5F32CA247088-02
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Katherine Jane Megquier
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,094
- **Award type:** 5
- **Project period:** 2020-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077203

## Citation

> US National Institutes of Health, RePORTER application 10077203, Advancing precision medicine through development of the canine comparative cancer model (5F32CA247088-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10077203. Licensed CC0.

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