Wu Kevin, Rodrigues Lucas, Post Gerald, Harvey Garrett, White Michelle, Miller Aubrey, Lambert Lindsay, Lewis Benjamin, Lopes Christina, Zou James
One Health Company, Palo Alto, CA, US.
Department of Biomedical Data Science, Stanford University, Stanford, US.
NPJ Precis Oncol. 2023 Jan 19;7(1):8. doi: 10.1038/s41698-023-00346-3.
Spontaneous tumors in canines share significant genetic and histological similarities with human tumors, positioning them as valuable models to guide drug development. However, current translational studies have limited real world evidence as cancer outcomes are dispersed across veterinary clinics and genomic tests are rarely performed on dogs. In this study, we aim to expand the value of canine models by systematically characterizing genetic mutations in tumors and their response to targeted treatments. In total, we collect and analyze survival outcomes for 2119 tumor-bearing dogs and the prognostic effect of genomic alterations in a subset of 1108 dogs. Our analysis identifies prognostic concordance between canines and humans in several key oncogenes, including TP53 and PIK3CA. We also find that several targeted treatments designed for humans are associated with a positive prognosis when used to treat canine tumors with specific genomic alterations, underscoring the value of canine models in advancing drug discovery for personalized oncology.
犬类的自发性肿瘤与人类肿瘤在基因和组织学上有显著相似之处，这使它们成为指导药物开发的有价值模型。然而，目前的转化研究实际证据有限，因为癌症治疗结果分散在各个兽医诊所，而且很少对狗进行基因组检测。在本研究中，我们旨在通过系统地表征肿瘤中的基因突变及其对靶向治疗的反应来扩大犬类模型的价值。我们总共收集并分析了2119只患肿瘤犬的生存结果，以及1108只犬的一个子集中基因组改变的预后影响。我们的分析确定了犬类和人类在几个关键癌基因（包括TP53和PIK3CA）中的预后一致性。我们还发现，几种为人类设计的靶向治疗药物，在用于治疗具有特定基因组改变的犬类肿瘤时，与良好的预后相关，这突出了犬类模型在推进个性化肿瘤学药物发现方面的价值。
