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Developmental Cancer Therapeutics

发育性癌症治疗

基本信息

批准号：
10377474
负责人：
Besim Ogretmen
金额：
$ 5.06万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10377474
关键词：
Advanced Glycosylation End Products African American Agonist Antineoplastic Agents Area Arrestins Award Biochemical Pathway Bioenergetics Biological Markers Biology Cancer Center Cancer Center Support Grant Catchment Area Cells Clinical Clinical Trials Collaborations Communities Complement Complex Development Doctor of Philosophy Education Enzymes Equipment Faculty Recruitment Fruit Funding Funding Mechanisms Future G-Protein-Coupled Receptors Geography Glycolipids Goals Grant Histone Deacetylase Human Immunooncology Infrastructure Interleukin-15 Investments Journals Laboratories Leadership Life Style Lipids Malignant Neoplasms Malignant neoplasm of liver Mediating Mediator of activation protein Medical Medicine Membrane Metabolic Metabolic Pathway Metabolic stress Metabolism Methyltransferase Minority Mitochondria Molecular Molecular Conformation Nature Non-Small-Cell Lung Carcinoma Oncogenic Oxidation-Reduction Oxidative Stress Pathway interactions Peer Review Pharmacy facility Phase I/II Trial Phase Ib/II Trial Phosphotransferases Physicians Pilot Projects Population Positioning Attribute Postdoctoral Fellow Prevention Productivity Prognostic Marker Prostaglandins Publications Publishing Recombinants Refractory Renal carcinoma Reporting Research Research Personnel Resource Sharing SECTM1 gene Science Scientific Advances and Accomplishments Scientist Seeds Seminal Series Signal Transduction South Carolina Sphingolipids Strategic Planning Structure Technology Therapeutic Therapeutic Agents Therapeutic Intervention Translating Translational Research Translations Tumor Cell Biology Tumor Immunity Ubiquitin Universities Ursidae Family base biological adaptation to stress biomarker development biomarker discovery cancer cell cancer chemoprevention cancer therapy career development clinical trial implementation college diagnostic biomarker drug development drug discovery early phase clinical trial extracellular graduate student inhibitor meetings member metabolomics multicatalytic endopeptidase complex novel novel therapeutics pre-clinical preclinical development preclinical trial programmed cell death protein 1 programs receptor socioeconomics sphingosine 1-phosphate sphingosine kinase translational pipeline tumor metabolism undergraduate student underserved community

项目摘要

DEVELOPMENTAL CANCER THERAPEUTICS: SUMMARY The Developmental Cancer Therapeutics (DCT) Program seeks to discover and characterize critical cancer- specific metabolic pathways, identify novel therapeutic agents, and translate discoveries into effective cancer therapies and chemoprevention strategies. Three common themes unite programmatic initiatives: 1) lipid signaling and metabolism, 2) cancer stress response pathways, and 3) drug discovery and early-phase clinical trials. Fundamental discoveries have been made in the identification and mechanistic understanding of sphingolipids, prostaglandins, membrane receptors, and extra-cellular factors involved in cancer cell signaling. Support from the Hollings Cancer Center (HCC) shared resources and collaborations within and across programs has led to identification of natural and synthetic compounds that target cancer metabolism, including inhibitors of sphingosine 1-phosphate and sphingosine kinase 2, which have moved to phase 1 and 2 trials in refractory renal and liver cancers (NCT01488513, NCT0176203, and NCT02939807). New compounds and biomarkers led to statewide opportunities for therapeutic intervention and prevention of human cancers impacting the HCC catchment area, including in the socioeconomically and geographically underserved African American communities. The program of 30 members is co-led by two exceptional scientists with distinct basic and clinical backgrounds who collaboratively build a synergistic program: Besim Ogretmen, PhD, a basic scientist pioneering discoveries in lipid biology and biomarker development, and Michael Lilly, MD, a practicing physician-scientist translating fundamental discoveries into clinical trials. The total peer-reviewed direct funding base, excluding career development and training grants is $4.8M, with 22 active NCI-funded projects ($3.5M), and a growing number of multi-institutional and programmatic awards (P20 GM103542; P01 CA203628; U54 MD010706, U54 CA210962). Rich collaborative research opportunities in DCT laboratories have enhanced the entire education and career development continuum, from undergraduates in minority colleges to graduate students, postdoctoral fellows, and junior clinical members (K12 CA157688). These cancer-focused efforts culminated in 238 publications since 2013, of which 34% represent intraprogrammatic, 37% interprogrammatic, and 67% multi-institutional collaborations, including 33 seminal discoveries and translational breakthroughs published in top-tier journals (IF >10) such as in N Engl J Med, Nature, Nat Comm, Sci Transl Med (2), Cell, Cell Metab, Mol Cell, JAMA (2), JCI (3), JCO (8), and Lancet Oncol (3). With investments in cutting edge technologies, targeted faculty recruitment, and new interprogrammatic team-based funding initiatives supported by new HCC leadership, the DCT Program is poised to advance scientific discovery, target identification and pre-clinical development, and clinical trials implementation in the HCC catchment area and beyond.

发展性癌症治疗：综述发展性癌症治疗(DCT)计划寻求发现和描述危重癌症-- 特定的代谢途径，确定新的治疗药物，并将发现转化为有效的癌症治疗和化学预防策略。三个共同主题统一了方案倡议：1)LID 信号和代谢，2)癌症应激反应途径，3)药物发现和早期临床审判。在识别和机理理解方面有了根本性的发现。鞘磷脂、前列腺素、膜受体和参与癌细胞信号传递的细胞外因子。来自霍林斯癌症中心(HCC)的支持，在内部和跨区域共享资源和合作这些计划导致了针对癌症新陈代谢的天然和合成化合物的识别，包括鞘氨醇1-磷酸和鞘氨醇激酶2的抑制剂，已在#年进入1期和2期试验难治性肾癌和肝癌(NCT01488513、NCT0176203和NCT02939807)。新化合物和生物标志物为全州范围内的人类癌症治疗干预和预防带来了机会影响最不发达国家集水区，包括在社会经济和地理服务不足的非洲美国社区。该计划由30名成员组成，由两名杰出的科学家共同领导，他们拥有不同的BASIC 和临床背景合作建立一个协同计划：贝西姆·奥格雷特曼，博士，基础在脂质生物学和生物标记物开发方面开创发现的科学家和迈克尔·礼来医学博士内科医生-科学家将基本发现转化为临床试验。经同行评审的直接资助总额基数，不包括职业发展和培训赠款为480万美元，有22个NCI资助的在建项目(350万美元)，以及越来越多的多机构和方案奖(P20 GM103542；P01 CA203628；U54 MD010706、U54 CA210962)。DCT实验室中丰富的协作研究机会增强了从少数民族院校本科生到研究生的整个教育和职业发展连续体学生、博士后研究员和初级临床成员(K12 CA157688)。这些专注于癌症的努力自2013年以来共出版了238份出版物，其中34%为方案内出版物，37%为方案间出版物， 67%的多机构合作，包括33项开创性发现和翻译突破发表在顶级期刊(IF&GT；10)上，如N Engl J Med，Natural，NAT Comm，Sci Transl Med(2)，Cell，细胞Metab、Mol Cell、JAMA(2)、JCI(3)、JCO(8)和Lancet Onol(3)。投资于尖端技术技术、有针对性的教师招聘和新的基于团队的跨计划筹资倡议在新的HCC领导层的支持下，DCT计划准备推进科学发现，目标是肝癌集水区的鉴定和临床前开发，以及临床试验的实施更远一点。