Sarcoma Predisposition in Dogs with a Comparative View to Human Orthologous Disease

Abstract

Sarcomas are malignant tumors arising from the embryonic mesodermal cell lineage. This group of cancers covers a heterogenous set of solid tumors arising from soft tissues or bone. Many features such as histology, biological behavior and molecular characteristics are shared between sarcomas in humans and dogs, suggesting that human sarcoma research can be informative for canine disease, and that dogs with sarcomas can serve as relevant translational cancer models, to aid in the understanding of human disease and cancer biology. In the present paper, risk factors for the development of sarcoma in dogs are reviewed, with a particular focus on recent advances in clinical genetics, and on the identification of simple and complex genetic risk factors with a comparison with what has been found in human orthologous disease.

The enzyme glutamate-cysteine ligase (GCL) is a target for ferroptosis induction in cancer

“…51 The canine cancer context is especially significant for the study of ferroptosis given that mesenchymal and undifferentiated cancer types, which are known to have heightened sensitivity to ferroptosis, are more prevalent in canine oncology than in the human setting. 52,53 Testing BSO across a panel of 31 available canine cancer cell lines 54 revealed a striking rate of ferroptotic response to GCL inhibition, with mesenchymal cancer cell lines showing greatest sensitivity, consistent with current understanding of ferroptosis susceptibility across cancer types (Fig. 6B).…”

Validation of ferroptosis in canine cancer cells to enable comparative oncology and translational medicine

“…[4][5][6] Of particular significance to ferroptosis, the incidence of mesenchymal tumors is far greater in the canine setting than among humans: while sarcomas are relatively rare in humans, roughly 15% of canine cancers are sarcomas. 7,8 This increased incidence translates directly into larger cohorts of patients with ferroptosis-relevant tumors as well as greater access to tissue samples, cell lines and other research tools representing ferroptosis-susceptible cancer states. 7,8 In addition to biological rationale, clinical trials in the veterinary oncologic setting afford a number of significant advantages for investigation of experimental therapeutics.…”

“…7,8 This increased incidence translates directly into larger cohorts of patients with ferroptosis-relevant tumors as well as greater access to tissue samples, cell lines and other research tools representing ferroptosis-susceptible cancer states. 7,8 In addition to biological rationale, clinical trials in the veterinary oncologic setting afford a number of significant advantages for investigation of experimental therapeutics. These features include ability to administer investigational agents in the pre-IND stage, high rates of clinical trial participation and patient compliance, rapid accrual of patients and accelerated timelines for trial completion, and high rates of consent for repeat biospecimen collection to enable in-depth PK-PD and biomarker studies aimed at demonstrating proof of mechanism.…”