Center for pediatric tumor cell atlas

儿科肿瘤细胞图谱中心

基本信息

批准号：
10016222
负责人：
STEPHEN Patrick HUNGER
金额：
$ 226.13万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
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：
2018-09-30 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10016222
关键词：
Address Adult Algorithms Atlases B-Cell Acute Lymphoblastic Leukemia Basic Science Biological Assay Biomedical Research Blood Vessels Blood specimen CAR T cell therapy California Cancer Center Cancer Patient Cell Nucleus Cell physiology Cells Cellular Structures Cessation of life Characteristics Childhood Chromatin Clinical Clinical Research Clonal Evolution Collaborations Communities Computer software Computing Methodologies Cytometry Data Databases Development Diagnosis Disease Disease Resistance Ecosystem Emerging Technologies Epigenetic Process Etiology Evaluation Evolution Fluorescent in Situ Hybridization Follow-Up Studies Freezing Genetic Glioma Grant Growth Heterogeneity Human Hypersensitivity Image Immune Immune system In Situ Infrastructure Knowledge Malignant - descriptor Malignant Childhood Neoplasm Malignant Neoplasms Maps Mediating Medical Methods Modality Molecular Mutagenesis Mutation Neoplasm Metastasis Neuroblastoma Non-Malignant Outcome Pathologic Pathway interactions Patients Pattern Pediatric Hospitals Pediatric Neoplasm Pediatric Oncology Pediatrics Pennsylvania Pharmacotherapy Phenotype Philadelphia Phylogenetic Analysis Phylogeny Population Proteins Public Health RNA Refractory Disease Research Research Personnel Resistance Resolution Site Small Nuclear RNA Source Spatial Distribution Specimen Standardization Technology Therapeutic Tissues Translational Research Trees Universities Visualization Xenograft procedure age group anticancer research base cancer imaging cancer therapy cancer type cell type chemotherapy childhood cancer mortality complex data computational pipelines computerized tools data sharing genome sequencing high risk improved insight molecular targeted therapies multiple omics neoplastic cell new therapeutic target open source outcome forecast precision oncology predictive marker pressure response single cell analysis single molecule stem transcriptome sequencing tumor tumor heterogeneity tumor initiation tumor microenvironment user-friendly whole genome

项目摘要

PROJECT SUMMARY - OVERALL Childhood Cancer is the second most common causes of childhood deaths. Cancers in children are highly distinct from those in adults. Causes, mechanisms and therapeutic approaches cannot be extrapolated from the study of adult malignancies. To impact the burden of pediatric cancers requires the specific study of pediatric cancers. We therefore propose the in depth characterization of three specific subtypes of pediatric malignancies which, together, account for over 50% of all pediatric cancer deaths: high grade glioma (pHGG), high risk neuroblastoma (NB), and very high risk acute lymphoblastic B-cell precursor leukemia (VHR-ALL). All three tumor types share a characteristic of typically initial response to therapy, followed by the emergence of resistance and refractory disease. We will map molecular and cellular changes in tumor cells, microenvironment and the immune system using comprehensive multi-dimensional single-cell and in situ technologies associated with two critical transitions: initial response, and emergence of resistant disease – both high-priority transitions. Treatment modalities will include standard chemotherapy, molecular targeted therapies and chimeric antigen receptor (CAR-) T cell therapy, capturing the cutting edge of current cancer therapy. The final product will impact global childhood cancer research in the following manner: 1) Tumor Atlases: atlases will provide a highly user friendly, publicly available, searchable database of the most comprehensive multi-omic, single cell analysis of the three most lethal childhood cancers. Molecular data will be richly annotated with access to additional pathological evaluation, clinical and outcomes data, and grant access to source data such tumor imaging. 2) Computational methods: in addition to the data, the critical computational tools and pipelines used in this project will be available to the research community. These include methods and pipelines for processing multi-omics and in situ data, inference of cancer phylogeny, inference of cell- and clone-specific pathways, methods for inferring cell-cell crosstalk, as well as database algorithms for the query, exploration and visualization of highly complex data. 3) Access to biospecimens for follow up studies: biospecimens collected in this project will be banked and made available to the biomedical research community. These include tissue sections, viably frozen specimen, and patient derived xenograft (PDX models). In summary, the proposed project will seek to address a major public health need in pediatrics, broadly impact the entire research community, and jumpstart target discovery based on a sophisticated understanding of the key molecular circuits that drive pediatric cancer.

项目摘要 - 总体儿童癌症是儿童死亡的第二大最常见原因。儿童中的癌症很高与成年人不同。原因，机制和治疗方法无法推断成人恶性肿瘤的研究。为了影响小儿癌的伯宁，需要对小儿取消。因此，我们提出了三种特定亚型小儿类型的深度表征恶性肿瘤共同占所有儿科癌症死亡的50％以上：高级神经胶质瘤（PHGG），高风险神经母细胞瘤（NB）和非常高风险的急性淋巴细胞B细胞前体白血病（VHR-ALL）。全部三种肿瘤类型具有通常对治疗的初始反应的特征，随后出现抵抗和难治性疾病。我们将绘制肿瘤细胞中的分子和细胞变化，使用综合多维单细胞和原位的微环境和免疫系统与两个关键转变相关的技术：初始反应和抗性疾病的出现 - 两个高优先级过渡。治疗方式将包括标准化疗，分子靶向疗法和嵌合抗原受体（CAR-）T细胞疗法，捕获当前癌症的尖端治疗。最终产品将以以下方式影响全球儿童癌症研究：1）肿瘤 ATLASE：ATLASE将提供一个高度用户友好，公开，可搜索的数据库三种最致命的儿童期癌症的全面多摩变，单细胞分析。分子数据将通过访问其他病理评估，临床和结果数据进行丰富的注释，并授予访问源数据此类肿瘤成像。 2）计算方法：除了数据外，关键该项目中使用的计算工具和管道将用于研究社区。这些包括用于处理多词和原位数据的方法和管道，推断癌症系统发育，细胞和克隆特异性途径的推断，推断细胞细胞串扰的方法以及数据库高度复杂数据的查询，探索和可视化算法。 3）访问生物测量后续研究：该项目中收集的生物测量将被存放并提供给生物医学研究社区。这些包括组织切片，有能力冷冻的样品和患者衍生的异种移植物（PDX型号）。总而言之，拟议的项目将寻求解决儿科的主要公共卫生需求，广泛影响整个研究社区，并基于复杂了解驱动小儿癌的关键分子回路。