1 of 3 Interdisciplinary Collaboratory for Enhancing Translational Therapeutics Utilizing Biologically, Immunologically, and Metabollically Relevant Models of Breast Cancer

1 of 3 利用乳腺癌的生物学、免疫学和代谢相关模型增强转化治疗的跨学科合作实验室

• 批准号: 8906052
• 负责人: WILLIAM JOSEPH MURPHY
• 金额: $ 58.09万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-15 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8906052
• 关键词: Accounting; Address; Adverse reactions; Age; Animal Cancer Model; Animal Model; Animals; Antigens; Applications Grants; Basic Science; Biological Assay; Biological Markers; Body fat; Breast Cancer Model; CD28 gene; Caloric Restriction; Cancer Model; Cancer Patient; Canis familiaris; Cell Culture Techniques; ChIP-seq; Characteristics; Clinic; Clinical; Clinical Trials; Data; Data Analyses; Databases; Demographic Aging; Development; Diet; Disease; Elderly; Environment; Epigenetic Process; Human; Image; Immune; Immunology; Immunotherapy; Inbred Mouse; Inbreeding; Individual; Inflammatory; Intraepithelial Neoplasia; Investigation; Laboratories; Link; Malignant Neoplasms; Mammary gland; Medical; Modeling; Modification; Molecular Genetics; Mus; Neoplasm Metastasis; Noninfiltrating Intraductal Carcinoma; Obese Mice; Obesity; Organ failure; Outcome; Overweight; Pathologic; Pathology; Patients; Phase I Clinical Trials; Phenotype; Population; Pre-Clinical Model; Preclinical Testing; Primates; Publications; Publishing; Radiation; Radioimmunotherapy; Regimen; Research Personnel; Sampling; Schools; Science; Site; Specific Pathogen Frees; Specific Pathogen-Free Organisms; Syndrome; Teaching Hospitals; Technology; Testing; Therapeutic; Toxic effect; Translational Research; Treatment Efficacy; Tumor-Derived; United Kingdom; Veterinary Medicine; Veterinary Schools; age effect; aged; anti-cancer therapeutic; anticancer research; base; cancer immunotherapy; cancer therapy; clinically relevant; collaboratory; cytokine; demographics; experience; feeding; germ free condition; improved; in vivo; malignant breast neoplasm; migration; mouse model; multidisciplinary; pandemic disease; phase I trial; pre-clinical; preclinical study; public health relevance; response; success; tool; tumor; tumor growth; tumor metabolism; tumor progression; tumorigenesis

 DESCRIPTION (provided by applicant): Current preclinical testing for cancer therapeutics generally consists of small animal (typically murine) studies followed by studies in primates to quickly assess gross toxicities prior to moving into phase I trials. To further complicate things, preclinical studies are often performed on young, lean, inbred, specific pathogen free (SPF) organisms which do not accurately reflect the demographic of the typical cancer patient. To address these discrepancies, our site is specifically proposing to utilize the unique environment at UC Davis which will combine basic research using murine models and large animal models, namely canines, from the UC Davis School of Veterinary Medicine. In addition to the multi-species comparisons, we are uniquely suited to address age and BMI related responses, which have not been extensively determined in any one model, yet alone confirmed across multiple species. We will extensively characterize and integrate responses based on a variety of assays and look for commonalities as predictable markers of outcomes focusing on differences with age and BMI to demonstrate that preclinical models need to be reflective of the cancer patient phenotype. Finally, we will be validating our findings using samples from both murine and canine tumor models, again another unique attribute specific to UC Davis which has access to canine cancer patients through the Veterinary Medical Teaching Hospital. Overall, our grant proposal ties into our collaborative proposal, which aims to link three specialized laboratories in a multi-disciplinary collaborative study to improve the utility of mouse cancer and tumor models for translational research. Each linked proposal will integrate imaging sciences, immunology, and pathobiology to advance current standard practices of using lean, young, SPF models and cell-culture-derived tumors into demographically appropriate mouse models with a shared focus on utilization of the mammary intraepithelial neoplasia outgrowth (MINO) model of human pre-cancer (provided by Dr. Cardiff's laboratory). The findings from our studies will together address the current incongruence between preclinical and clinical outcomes, and also demonstrate means to overcome these limitations through defining more appropriate models that will increase translatability into the clinic.