Validation of ferroptosis in canine cancer cells to enable comparative oncology and translational medicine
Priya ChatterjiiD, Gang XingiD, Laura Furst, Krishna Dave, Qiong ZhouiD, Daniel V. LaBarberaiD, Douglas H. ThammiD, John K. EatoniD, Mathias J. WaweriD, Vasanthi S. ViswanathaniD
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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