Singer SPORE Supplement

歌手 SPORE 补充品

基本信息

批准号：
10912166
负责人：
SAMUEL SINGER
金额：
$ 91.86万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10912166
关键词：
Address Adult Advisory Committees Affinity Animal Model Animals Autophagocytosis Award Bioinformatics Biological Specimen Banks Biology Biometry Blood Banks CDK4 gene CRISPR/Cas technology Cell Line Cell Survival Cells Childhood Clinical Clinical Investigator Clinical Research Clinical Trials Clinical Trials Unit Clustered Regularly Interspaced Short Palindromic Repeats Collaborations Collection Combined Modality Therapy Communication Communities Complement Complex Cyclin-Dependent Kinase Inhibitor 2A Data Data Set Databases Development Diagnosis Disease Drug Targeting ETV1 gene EZH2 gene Education Engineering Ensure Epigenetic Process Ethnic Population Evaluation FRAP1 gene Fibroblast Growth Factor Receptors Gastrointestinal Stromal Tumors Generations Genes Genetic Genetic Predisposition to Disease Goals Growth Human Image Imatinib Immune Immunocompetent In Vitro Individual Institution Integrins Laboratories Laboratory Research Link MDM2 gene MEKs Malignant Fibrous Histiocytoma Messenger RNA Methodology Modeling Molecular Molecular Analysis Molecular Genetics Molecular Profiling Monitor Monoclonal Antibodies Morbidity - disease rate Mus Myxoid Malignant Fibrous Histiocytoma Oncogenic Open Reading Frames Operative Surgical Procedures Outcome PIK3CG gene Participant Pathologic Pathway interactions Patient advocacy Patients Performance Personnel Management Pharmaceutical Preparations Phosphoproteins Phosphotransferases Population Prognosis Protein Isoforms Proteins Proteomics Publishing RNA Helicase Research Research Personnel Research Project Grants Research Support Resistance Resources Role Sampling Signal Pathway Signal Transduction Soft tissue sarcoma Structure Systemic Therapy TP53 gene Testing Tissue Banks Tissue Sample Tissues Translating Translational Research Translations Update Validation Xenograft procedure advanced disease biomarker identification blood resource career clinical application design efficacy evaluation functional genomics human model human tissue in vitro activity in vivo in vivo Model inhibitor inhibitor therapy insight mTOR Inhibitor mTOR inhibition member molecular pathology mortality mouse model multidisciplinary mutation screening new therapeutic target novel novel strategies novel therapeutic intervention novel therapeutics outcome prediction patient derived xenograft model pre-clinical preclinical evaluation predicting response predictive marker programs prospective quality assurance racial population recruit research clinical testing resistance mechanism resistance mutation response sarcoma senescence synovial sarcoma targeted sequencing targeted treatment therapeutic development therapeutic target therapy development therapy resistant tissue preparation tissue resource translational cancer research treatment response treatment strategy tumor tumor DNA

项目摘要

ABSTRACT The long-term goal of the SPORE in Soft Tissue Sarcoma is to reduce the morbidity and mortality from soft tissue sarcoma by developing therapies targeted to specific molecular, genetic, epigenetic, and signaling pathway alterations or specific sarcoma type and subtype. To pursue this, we will focus our efforts on 4 broad translational research objectives: 1. Define shared and type-specific molecular mechanisms of sarcomagenesis to identify new rational therapeutic targets; 2. Define mechanisms of resistance to targeted therapies; 3. Clinically validate new therapeutic targets and treatments in soft tissue sarcoma patients and facilitate the development, recruitment, and application of clinical trials that serve both the adult and pediatric populations; 4. Discover specific molecular alterations and new biomarkers that predict outcome and response to targeted therapy. To achieve these goals, we have marshaled an integrated, multidisciplinary group of basic and clinical investigators, all armed with a unique resource, a clinicopathologic and outcomes database prospectively collected over a 35-year period. This database now contains data for over 11,840 patients treated for soft tissue sarcoma at MS. The database is linked to an extensive sarcoma tissue/blood bank, which in turn is linked to an extensive multi-platform molecular genetic and epigenetic dataset and a collection of primary sarcoma cell lines and mouse xenograft/PDX models of human sarcoma. The SPORE is structured around 4 research projects, 4 cores, and career enhancement and developmental research programs. Each research project focuses on three or more of the 4 broad translational research goals listed above. RP-1 (GIST Resistance) aims to identify new therapeutic targets and develop new treatment strategies for imatinib- resistant GIST, including strategies for the largely pediatric subset with SDH-deficient GIST. RP-2 (CDK4 Targeting) seeks to identify a pre-treatment biomarker predictive of prolonged clinical response to CDK4 inhibitor therapy and to find drugs that can be combined with CDK4 inhibition to synergistically augment the senescence response. RP-3 (Oncogenic Pathways) seeks to determine the efficacy and molecular effects of inhibitors of mTOR, PI3K, MEK, and oncogenic translation (eIF4A), alone and in combination, in myxofibrosarcoma and undifferentiated pleomorphic sarcoma to develop new targeted treatment strategies. RP-4 (Functional Genomic Screens) will perform CRISPR-based functional genomic screens to uncover epigenetic and genetic vulnerabilities in synovial sarcoma with the aim of discovering drug targets for preclinical and clinical evaluation.

抽象的软组织肉瘤中孢子的长期目标是降低来自软组织肉瘤通过开发针对特定分子，遗传，表观遗传和信号通路改变或特定的肉瘤类型和亚型。为了追求这一点，我们将集中精力在4个广泛的转化研究目标上的努力：1。定义共享和类型特定的分子肉体作用的机制，以识别新的理性治疗靶标； 2。定义机制对靶向疗法的抵抗力； 3。临床验证软软的新治疗靶标和治疗组织肉瘤患者并促进临床试验的开发，招募和应用服务成人和小儿种群； 4。发现特定的分子改变和新的变化预测结果和对靶向治疗的反应的生物标志物。为了实现这些目标，我们有编制了一个综合的，多学科的基本和临床研究人员，所有这些都武装着独特的资源，一种临床病理学和结果数据库，可预期收集35年时期。现在，该数据库包含在MS上接受软组织肉瘤治疗的11,840例患者的数据。该数据库链接到广泛的肉瘤组织/血库，这又与广泛有关多平台分子遗传和表观遗传数据集以及一系列原发性肉瘤细胞系和小鼠异种移植物/人类肉瘤的PDX模型。孢子是围绕4个研究项目结构的 4个核心以及职业增强和发展研究计划。每个研究项目都集中在上面列出的4个广泛的翻译研究目标中，有三个或多个。 RP-1（要点抵抗）的目标为了确定新的治疗靶标并为抗伊马替尼的要点制定新的治疗策略，包括具有SDH缺陷的GIST的主要儿科子集的策略。 RP-2（CDK4靶向）试图确定对延长CDK4抑制剂的临床反应的预测前生物标志物预测治疗并找到可以与CDK4抑制相结合以协同增强的药物衰老反应。 RP-3（致癌途径）旨在确定功效和分子效应 MTOR，PI3K，MEK和致癌翻译（EIF4A）的抑制剂，单独和组合粘纤维肉瘤和未分化的多形性肉瘤以开发新的靶向治疗策略。 RP-4（功能基因组筛选）将执行基于CRISPR的功能基因组筛选在滑膜肉瘤中发现表观遗传和遗传脆弱性，目的是发现药物临床前和临床评估的目标。

项目成果

期刊论文数量（158）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

PEComa-like Neoplasms Characterized by ASPSCR1-TFE3 Fusion: Another Face of TFE3-related Mesenchymal Neoplasia.

DOI：
10.1097/pas.0000000000001894
发表时间：
2022-08-01
期刊：
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
影响因子：
5.6
作者：
Argani, Pedram;Wobker, Sara E.;Gross, John M.;Matoso, Andres;Fletcher, Christopher D. M.;Antonescu, Cristina R.
通讯作者：
Antonescu, Cristina R.

ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements.

DOI：
10.1002/gcc.22454
发表时间：
2017-06
期刊：
Genes, chromosomes & cancer
影响因子：
0
作者：
Kao YC;Sung YS;Chen CL;Zhang L;Dickson BC;Swanson D;Vaiyapuri S;Latif F;Alholle A;Huang SC;Hornick JL;Antonescu CR
通讯作者：
Antonescu CR

Soft tissue tumors characterized by a wide spectrum of kinase fusions share a lipofibromatosis-like neural tumor pattern.

DOI：
10.1002/gcc.22877
发表时间：
2020-10
期刊：
Genes, chromosomes & cancer
影响因子：
0
作者：
Kao YC;Suurmeijer AJH;Argani P;Dickson BC;Zhang L;Sung YS;Agaram NP;Fletcher CDM;Antonescu CR
通讯作者：
Antonescu CR

Rocaglates as Antivirals: Comparing the Effects on Viral Resistance, Anti-Coronaviral Activity, RNA-Clamping on eIF4A and Immune Cell Toxicity.

DOI：
10.3390/v14030519
发表时间：
2022-03-03
期刊：
Viruses
影响因子：
0
作者：
Obermann W;Friedrich A;Madhugiri R;Klemm P;Mengel JP;Hain T;Pleschka S;Wendel HG;Hartmann RK;Schiffmann S;Ziebuhr J;Müller C;Grünweller A
通讯作者：
Grünweller A

Head and neck rhabdomyosarcoma with TFCP2 fusions and ALK overexpression: a clinicopathological and molecular analysis of 11 cases.