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Enhancing the dog as a model for human cancers: from genome sequence towards clinical trials.

增强狗作为人类癌症模型的作用：从基因组序列到临床试验。

基本信息

批准号：
10237356
负责人：
Kerstin Lindblad-Toh
金额：
$ 38.58万
依托单位：
UPPSALA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-06 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10237356
关键词：
Adopted Affect Alleles Antigen-Antibody Complex Blood specimen Cancer Model Canis familiaris Catalogs Chromium Classification Clinical Clinical Trials Code Collaborations Collection Complex Copy Number Polymorphism Data Development Disease Progression Elements Environment Environmental Risk Factor Etiology Evaluation Evolution Female Future Gene Family Gene Frequency Genes Genetic Risk Genetic study Genome Genomic Segment Germ Lines German population Histologic Histology Human Human Genome Immune Immune response Immunocompetent Impairment Individual Laboratory Research Longevity Lymphoma Major Histocompatibility Complex Malignant - descriptor Malignant Neoplasms Mammals Mammary Neoplasms Methodology MicroRNAs Modeling Molecular Mus Mutation Mutation Analysis Oncology Outcome Platinum Population Prognosis Relapse Research Resources Rodent Sampling Scandinavia Scandinavian System T-Cell Receptor Genes Techniques Time Toxic effect Translations Treatment outcome Tumor Subtype Untranslated RNA Variant Work cancer clinical trial cancer genome cancer subtypes cancer therapy cancer type cell free DNA comparative dog genome drug development exome genetic variant genome annotation genome wide association study human data improved malignant breast neoplasm molecular phenotype novel novel anticancer drug osteosarcoma sample collection side effect structural genomics transcriptome sequencing treatment strategy tumor whole genome

项目摘要

SUMMARY The domestic dog has become increasingly useful as a comparative spontaneous cancer model to study genetic and environmental risk factors as well as for easing the transition between rodent and human clinical trials for novel cancer therapies. The many similarities between various cancer types affecting humans and dogs and the spontaneous development of these cancers in immune competent canine individuals living in a shared environment with us suggest a common aetiology. The shorter lifespan of dogs and the shorter time to relapse after cancer treatment allows data regarding efficacy, short and long term toxicity and side effects of novel cancer drugs to be generated in years rather than decades as in human clinical trials. However, certain limitations need to be overcome to make full use of the dog model. Slightly different classification systems for common cancers limit translation of data and clinical outcome from dog to human. The canine genome and annotation, especially that of complex immune gene families, could be improved to allow a more careful and correct comparison with the human genome and immune response, a key factor in cancer development and treatment. Using novel long-read sequencing techniques, we will generate a platinum CanFam4.0 genome and improved information of both gene and variant annotation for an old healthy female German shepherd. In addition, we will specifically focus on canine mammary tumors, lymphoma and osteosarcoma where improved models would benefit human studies, and the canine forms are diverse and only partly characterized. Since the molecular sub-classifications used in human cancers are not yet used for these canine cancers, we plan to characterize these tumor types in the dog population using several approaches to meet human standards. We will further set up a Scandinavian-wide veterinary oncology network for research collaboration, increased use of the dog as a model. We will perform repeated blood sampling from dogs with malignant mammary tumors to allow the study of tumor evolution and progression. All of this work will lay the groundwork to enable more useful and efficient future clinical trials.

总结