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.

抽象的 对癌症研究的新方法的需求未满足，包括改进的模型系统。宠物狗 是转化癌症研究最有希望的自然模型之一。他们分享我们的 与人类癌症具有明显的临床，组织学和基因组相似性的环境和发展癌症。 我们建议使用新的基因组技术和直接dog所有者的方法来克服现有 犬模型的局限性。 为此，我们将使用新的液体活检技术，这使得可以对肿瘤进行测序 来自血液样本的无细胞DNA中的外侧，从而更深入地了解肿瘤 没有侵入性活检的基因组学。这些微创采样技术的力量最大 在应用于非常大的临床样本中。家庭狗，其环境与人类共享 肿瘤基因组学类似于人类癌症，提供无与伦比的模型来组装 大小的临床集足以确认已知遗传途径的相关性，并确定新的 一个。 我们建议结合无细胞的DNA测序的力量，公民科学家宠物主人的热情， 以及兽医的临床经验。我们将创建一个研究门户，以收集有关 成千上万的癌症狗及其环境和环境的诊断，治疗和结果 生活方式。我们还将开发新的计算方法，以识别之间的基因组相似性 犬和​​人类癌。这些犬和人类突变曲线的比较将使匹配 基于遗传途径的人类癌症亚型的犬类癌亚型，促进犬试验 提前人类临床研究。我们的目标是： 目标1。开发软件，使用基因组数据识别人类癌症的犬类模型和 全面的组织学盲分析方法。 AIM 2。在狗中开发和优化无细胞的DNA采样和测序方法，包括 超低通的整个基因组测序和整个外显子组测序。 目标3。实施直接dog所有者智能手机应用程序来收集和验证详细的临床，并且 环境数据与数千只狗配对的血液样本配对。 通过将基因组测序和新的液体活检技术的力量结合在一起 从基因组中反映人类的物种的物种中收集大量样品，我们 项目将改变转化癌症研究和精密医学的规模和范围。