Transforming family dogs into a powerful and accessible model for human cancer

将家养狗转变为强大且易于使用的人类癌症模型

• 批准号: 10478250
• 负责人: Elinor Karlsson
• 金额: $ 61.09万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10478250
• 关键词: Address; Benchmarking; Biological Models; Biopsy; Blood; Blood specimen; Canis familiaris; Catalogs; Chemical Exposure; Clinical; Clinical Research; Clinical Trials; Code; Collection; Community Clinical Oncology Program; Computer software; Computing Methodologies; DNA sequencing; Data; Development; Diagnosis; Diagnostic; Dog family; Environment; Evolution; Gene Mutation; Genes; Genetic; Genomics; Gold; Histologic; Histology; Human; Inherited; Institutes; Learning; Life Style; Longitudinal Studies; Malignant Neoplasms; Medical center; Medicine; Methods; Modeling; Molecular Profiling; Mutate; Mutation; Oncology; Operative Surgical Procedures; Pathway interactions; Patients; Pattern; Phenotype; Records; Reporting; Research; Research Design; Research Personnel; Resources; Risk; Sampling; Scientist; Silicones; Techniques; Technology; Testing; Therapeutic; Time; Translating; Treatment outcome; United States; Untranslated RNA; Veterinarians; analysis pipeline; anticancer research; base; blind; cancer genomics; cancer subtypes; canine model; cell free DNA; chemotherapy; citizen science; classifier algorithm; cohort; comparative; comparative genomics; driver mutation; exome; exome sequencing; experience; genetic risk factor; genome sequencing; genomic data; genomic platform; human data; human model; improved; liquid biopsy; minimally invasive; new technology; novel strategies; open source; precision medicine; predicting response; programs; response; smartphone Application; software development; supervised learning; targeted treatment; tool; translational cancer research; translational model; tumor; tumor exome; whole genome

ABSTRACT There is an unmet need for novel approaches to cancer research, including improved model systems. Pet dogs are among the most promising natural models for translational cancer research. They share our environment and develop cancers with clear clinical, histological, and genomic similarities to human cancer. We propose to use new genomic technology and a direct-to-dog-owner approach to overcome existing limitations of the canine model. To accomplish this, we will use new liquid biopsy technology, which makes it possible to sequence tumor exomes in circulating cell-free DNA from a blood sample, and thus achieve deeper understanding of tumor genomics without invasive biopsies. The power of these minimally invasive sampling technologies is greatest in application to very large sets of clinical samples. Family dogs, whose environments are shared with humans and for which tumor genomics are similar to human cancers, offer an unparalleled model in which to assemble clinical sets of size sufficient both to confirm the relevance of known genetic pathways, and to identify new ones. We propose to combine the power of cell-free DNA sequencing, the enthusiasm of citizen-scientist pet owners, and the clinical experience of veterinarians. We will create a research portal for collection of information on diagnosis, treatment, and outcome for thousands of dogs with cancer, as well as their environment and lifestyle. We will also develop new computational methodologies to identify genomic similarities between canine and human cancers. Comparison of these canine and human mutational profiles will enable matching of canine cancer subtypes with human cancer subtypes based on genetic pathways, facilitating canine trials to advance human clinical studies. We aim to: Aim 1. Develop software to Identify canine models for human cancers using genomic data and comprehensive, histology-blind analysis approach. Aim 2. Develop and optimize cell-free DNA sampling and sequencing methods in dogs, including ultra-low-pass whole genome sequencing and whole exome sequencing. Aim 3. Implement a direct-to-dog-owner smartphone app to collect and validate detailed clinical, and environmental data, paired with blood samples, for thousands of dogs. By combining the power of genome sequencing and new liquid biopsy technology with the opportunity to collect large sets of samples from a species whose cancers are genomically reflective of those in humans, our project will transform the scale and scope of translational cancer research and precision medicine.

摘要 对癌症研究的新方法，包括改进的模型系统，存在未满足的需求。宠物狗 是转化型癌症研究中最有前途的自然模型之一。他们分享我们的 环境和发展癌症与人类癌症具有明确的临床，组织学和基因组相似性。 我们建议使用新的基因组技术和直接对狗主人的方法来克服现有的 犬模型的局限性。 为了实现这一目标，我们将使用新的液体活检技术，这使得肿瘤序列成为可能。 从血液样本中循环无细胞DNA中的外显子组，从而实现对肿瘤的更深入了解 不需要侵入性活检的基因组学这些微创采样技术的威力是最大的 应用于非常大的临床样品组。家庭狗，它们的环境与人类共享 并且肿瘤基因组学与人类癌症相似，提供了一个无与伦比的模型， 临床集的大小足以证实已知的遗传途径的相关性，并确定新的 一个 我们建议联合收割机无细胞DNA测序的力量，公民科学家宠物主人的热情， 和兽医的临床经验。我们将建立一个研究门户网站，收集以下信息： 诊断，治疗和结果的数千只狗与癌症，以及他们的环境和 生活方式我们还将开发新的计算方法，以确定基因组之间的相似性， 犬类和人类的癌症这些犬和人突变谱的比较将使匹配成为可能。 犬癌症亚型与人类癌症亚型基于遗传途径，促进犬试验， 推进人类临床研究。我们的目标是： 目标1.开发软件，利用基因组数据识别人类癌症的犬模型， 全面的组织学盲法分析方法。 目标2.开发和优化犬的无细胞DNA采样和测序方法，包括 超低通全基因组测序和全外显子组测序。 目标3.实施一个直接面向狗主人的智能手机应用程序，以收集和验证详细的临床资料， 环境数据，与血液样本配对，为数千只狗。 通过结合基因组测序和新的液体活检技术的力量， 从一个物种中收集大量的样本，这些物种的癌症在基因组上反映了人类的癌症，我们的 该项目将改变转化癌症研究和精准医学的规模和范围。