Chatterji Priya, Xing Gang, Furst Laura, Dave Krishna, Zhou Qiong, LaBarbera Daniel V, Thamm Douglas H, Eaton John K, Wawer Mathias J, Viswanathan Vasanthi S
Kojin Therapeutics, 451 D Street, Suite 502, Boston, MA 02210.
The CU Anschutz Center for Drug Discovery, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 E. Montview Blvd, Aurora, CO 80045.
bioRxiv. 2024 Apr 30:2024.04.28.591561. doi: 10.1101/2024.04.28.591561.
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.
铁死亡是一种细胞死亡机制，作为新癌症疗法开发的潜在基础已引起广泛关注。在常用于转化和临床前开发的物种中验证铁死亡生物学特性是推进此类铁死亡调节药物的必要基础。在此，我们证明犬癌细胞对多种铁死亡诱导扰动表现出敏感性，其方式与人类癌细胞难以区分，并重现了在人类环境中观察到的不同肿瘤类型的铁死亡反应特征模式。本文提供的基础将犬确立为铁死亡相关的疗效和毒理学模型，并为利用犬类比较肿瘤学范式加速针对人类癌症患者的铁死亡诱导药物开发创造了新机会。
