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

Chatterji, P.; Xing, G.; Furst, L.; Dave, K.; Zhou, Q.; LaBarbera, D. V.; Thamm, D. A.; Eaton, J. K.; Wawer, M. J.; Viswanathan, V. S.

2024-04-30 cancer biology
10.1101/2024.04.28.591561 bioRxiv
Show abstract

Ferroptosis is a cell death mechanism that has attracted significant attention as a potential basis for the development of new cancer therapies. Validation of ferroptosis biology in species commonly used in translation and pre-clinical development is a necessary foundation for enabling the advancement of such ferroptosis modulating drugs. Here, we demonstrate that canine cancer cells exhibit sensitivity to a wide range of ferroptosis-inducing perturbations in a manner indistinguishable from human cancer cells, and recapitulate characteristic patterns of ferroptotic response across tumor types seen in the human setting. The foundation provided herein establishes the dog as a relevant efficacy and toxicology model for ferroptosis and creates new opportunities to leverage the canine comparative oncology paradigm to accelerate the development of ferroptosis-inducing drugs for human cancer patients.

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