Sommer Breann C, Dhawan Deepika, Ratliff Timothy L, Knapp Deborah W
Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN, USA.
Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA.
Bladder Cancer. 2018 Apr 26;4(2):149-159. doi: 10.3233/BLC-170145.
The development of targeted therapies and the resurgence of immunotherapy offer enormous potential to dramatically improve the outlook for patients with invasive urothelial carcinoma (InvUC). Optimization of these therapies, however, is crucial as only a minority of patients achieve dramatic remission, and toxicities are common. With the complexities of the therapies, and the growing list of possible drug combinations to test, highly relevant animal models are needed to assess and select the most promising approaches to carry forward into human trials. The animal model(s) should possess key features that dictate success or failure of cancer drugs in humans including tumor heterogeneity, genetic-epigenetic crosstalk, immune cell responsiveness, invasive and metastatic behavior, and molecular subtypes (e.g., luminal, basal). While it may not be possible to create these collective features in experimental models, these features are present in naturally-occurring InvUC in pet dogs. Naturally occurring canine InvUC closely mimics muscle-invasive bladder cancer in humans in regards to cellular and molecular features, molecular subtypes, biological behavior (sites and frequency of metastasis), and response to therapy. Clinical treatment trials in pet dogs with InvUC are considered a win-win scenario; the individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to translate to better treatment outcomes in humans. This review will provide an overview of canine InvUC, the similarities to the human condition, and the potential for dogs with InvUC to serve as a model to predict the outcomes of targeted therapy and immunotherapy in humans.
靶向治疗的发展和免疫治疗的复兴为显著改善浸润性尿路上皮癌（InvUC）患者的预后提供了巨大潜力。然而，优化这些治疗至关重要，因为只有少数患者能实现显著缓解，且毒性很常见。鉴于治疗的复杂性以及需要测试的可能药物组合不断增加，需要高度相关的动物模型来评估和选择最有前景的方法推进到人体试验中。动物模型应具备决定癌症药物在人体中成败的关键特征，包括肿瘤异质性、遗传-表观遗传相互作用、免疫细胞反应性、侵袭和转移行为以及分子亚型（如管腔型、基底型）。虽然在实验模型中可能无法创造出所有这些共同特征，但这些特征存在于宠物狗自然发生的InvUC中。自然发生的犬类InvUC在细胞和分子特征、分子亚型、生物学行为（转移部位和频率）以及对治疗的反应方面与人类的肌肉浸润性膀胱癌密切相似。对患有InvUC的宠物狗进行临床治疗试验被认为是一种双赢的情况；每只狗都能从有效治疗中受益，预期结果将有助于其他狗，并且预计研究结果能转化为人类更好的治疗效果。本综述将概述犬类InvUC、与人类疾病的相似之处，以及患有InvUC的狗作为预测人类靶向治疗和免疫治疗结果模型的潜力。
