He Chang, Rottenberg Sven
Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland.
Vet Sci. 2025 Aug 26;12(9):815. doi: 10.3390/vetsci12090815.
In vitro culture systems have advanced cancer biology, particularly through 2D and 3D tumor cultures. These have answered numerous scientific inquiries and propelled human oncologic research, with growing recognition of their potential to improve cancer treatment in companion animals, specifically cats and dogs. These species develop cancer spontaneously, closely resembling specific human cancer subtypes. For example, canine and feline mammary tumors are especially valuable for studying tumor biology. In vitro models from these tumors therefore offer a unique opportunity for veterinary cancer research. Recent 3D cell culture advancements provide promising platforms for predicting therapeutic responses in human cancer and may be applied to mammary tumors in animals. However, while limitations in fully recapitulating in vivo conditions and predicting chemotherapy response have been observed in colorectal tumoroids, similar challenges are emerging in mammary and breast tumors. In particular, canine mammary tumors and human breast cancers share critical heterogeneity and microenvironmental factors usually inadequately modeled in vitro. This review critically examines the predictivity of 3D mammary tumoroids from humans and companion animals, highlighting challenges related to stromal and immune cell preservation, reproducibility, and the translational gap between in vitro findings and clinical outcomes. We propose future directions to optimize these models for both comparative oncology and veterinary-specific applications.
体外培养系统推动了癌症生物学的发展，特别是通过二维和三维肿瘤培养。这些培养系统解答了众多科学问题，推动了人类肿瘤学研究，人们也越来越认识到它们在改善伴侣动物（特别是猫和狗）癌症治疗方面的潜力。这些物种会自发患上癌症，与特定的人类癌症亚型极为相似。例如，犬类和猫类乳腺肿瘤对于研究肿瘤生物学特别有价值。因此，来自这些肿瘤的体外模型为兽医癌症研究提供了独特的机会。最近的三维细胞培养进展为预测人类癌症的治疗反应提供了有前景的平台，也可能应用于动物的乳腺肿瘤。然而，虽然在结直肠类肿瘤中已观察到在完全重现体内条件和预测化疗反应方面存在局限性，但在乳腺和乳腺癌中也出现了类似的挑战。特别是，犬类乳腺肿瘤和人类乳腺癌具有关键的异质性和微环境因素，而这些因素在体外通常无法得到充分模拟。本综述批判性地审视了来自人类和伴侣动物的三维乳腺类肿瘤的预测性，强调了与基质和免疫细胞保存、可重复性以及体外研究结果与临床结果之间的转化差距相关的挑战。我们提出了未来的方向，以优化这些模型用于比较肿瘤学和兽医特定应用。
