Lay Abstract:
Mast cell tumor (MCT) is the most common malignant canine skin tumor, which accounts
for 16~21% of all skin tumors. Although all breeds have a potential risk for developing MCTs,
many pure breeds(e.g., Boxers, Boston Terriers) are predisposed, resulting in a high disease
incidence. Despite the efforts, clinical management decisions are difficult because of the
challenging biological behavior of some MCTs and the inaccuracy of the predictive and prognostic
biomarkers or other molecular descriptors (i.e., c-KIT staining pattern and mutation status, KI-67,
AgNOr). While surgery is the mainstay of managing canine MCTs, toceranib phosphate (Palladia)
showed clinical benefits to those MCTs that require chemotherapy. However, most will develop
acquired resistance within months of starting the treatment. Currently, there are no means of
identification of treatment resistance apart from clinical characteristics, which usually capture the
relapse late, when the disease is already disseminated. In addition, most procedures used for
monitoring patients with MCT require sedation or general anesthesia.
Early disease progression detection by quantifying minimal residual disease is thus an
unmet clinical need. The development of such an assay could significantly affect disease
management, improve patient outcomes and welfare, and help emerge novel therapeutic targets
through better patient stratification. Next-generation sequencing (NGS) based liquid biopsy can
measure tumor burden and minimal residual disease in a minimally invasive way, such as blood
sampling, utilizing different tumor-related entities (e.g., cf/ctDNA, exosomes). Although liquid
biopsy has been proposed for screening and initial results for monitoring have been published,
the clinical utility of liquid biopsy for canine MCTs has yet to be established. The proposed study
would open a critical new area of monitoring MCT patients and could significantly improve their
quality of life and significantly impact veterinary oncology.