Drug Discovery, Delivery, and Translational Therapeutics Research Program

药物发现、递送和转化治疗研究计划

基本信息

批准号：
10204892
负责人：
JILL MARIE KOLESAR
金额：
$ 3.2万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-08 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10204892
关键词：
Adjuvant Appalachian Region Automobile Driving Basic Science Binding Proteins Bioinformatics Biological Markers Biometry Cancer Center Cancer Center Support Grant Cancer Control Cancer Intervention Cancer Patient Carcinogen exposure Catchment Area Cellular biology Characteristics Clinic Clinical Cancer Center Clinical Data Clinical Pathology Clinical Protocols Clinical Trials Collaborations Colon Colon Carcinoma Community Outreach Complex DNA Development Devices Diagnosis Diagnostic Trial Direct Costs Dissemination and Implementation EIF4EBP1 gene Early Therapeutic-Clinical Trials Network Early identification Engineering Enrollment Environmental Carcinogens Epigenetic Process Eukaryotic Initiation Factors Evaluation Ewings sarcoma Fatty Acids Fli-1 protein Frequencies Funding Genomic Instability Geography Goals Grant Health Services Accessibility High-Risk Cancer Hydroxychloroquine Informatics Infrastructure International Intervention Investigation Investigational New Drug Application Investments Kentucky Knowledge Laboratory Research Lead Libraries Ligands Ligase Link Lung Malignant Neoplasms Malignant neoplasm of lung Metabolism Mission Molecular Molecular Abnormality Molecular Target Mutation Natural Product Drug Natural Products Ovarian PAWR gene Participant Pathology Patients Pharmacologic Substance Pharmacy facility Phenotype Phosphorylation Physicians Population Precision Medicine Initiative Preclinical Testing Protocols documentation Publications Publishing Reporting Research Research Personnel Resources Role Science Scientist Signal Transduction Socioeconomic Status Squamous Cell Lung Carcinoma Therapeutic Therapeutic Agents Therapeutic Human Experimentation Therapeutic Trials Translating Translations Universities Vision Work Writing anticancer activity anticancer research anticancer treatment biomarker discovery cancer biomarkers cancer cell cancer clinical trial cancer genomics cancer prevention cancer subtypes cancer therapy clinical development clinical implementation cohesion college cross disciplinary program data management design drug candidate drug development drug discovery druggable target early phase clinical trial evidence base exome sequencing individual patient inhibitor/antagonist innovation inter-institutional malignant breast neoplasm member metabolomics molecular marker mutational status neoplasm registry new therapeutic target novel novel anticancer drug novel marker novel therapeutics phenotypic biomarker pre-clinical precision medicine programs recruit repository research facility screening senior faculty synergism targeted agent targeted biomarker targeted treatment translational study treatment response treatment trial tumor

项目摘要

PROJECT SUMMARY/ABSTRACT The Drug Discovery, Delivery and Translational Therapeutics (DT) Program at the Markey Cancer Center (MCC) is scientifically focused on identifying novel targets and biomarkers and discovering and developing new drugs targeting these biomarkers. The MCC catchment area population has both a high cancer risk related to excessive carcinogen exposure and lack of access to cutting-edge clinical trials due to geographical isolation and poor socioeconomic status. The DT program vision is to understand the unique molecular and phenotypic markers of cancer in Kentucky as well as barriers to accessing care and integrate that knowledge to inform drug discovery, development, and delivery of early phase clinical trial efforts for a hard-to-reach Appalachian Kentucky population. MCC investigators are international leaders in biomarker discovery (Theme 1) with ongoing translational studies including more than 600 participants, evaluating the role of environmental carcinogens and identifying biomarkers of lung cancer. DT pharmaceutical scientists work to discover and develop new anticancer agents targeting identified mutations and phenotypes (Theme 2), partnering with Cancer Cell Biology and Signaling (CS) and Genomic Instability, Epigenetics, and Metabolism (GEM) program members. For example, a novel modulator of 4E-BP1 phosphorylation, a validated colon cancer target, was identified from the Appalachian natural products repository. DT investigators lead clinical trials focusing on cancers relevant to the catchment area (Theme 3) and have enrolled more than 500 patients to lung, colon and ovarian interventional treatment and diagnostic trials. They regularly partner with Cancer Prevention and Control (CP), CS and GEM program members to inform and advance MCC basic science, for example, translating early identification of the anticancer activity of PAR-4 in CS to clinical trials focused on a PAR-4 secratagogue. DT is a cross-disciplinary program of 47 investigators from 6 colleges and 18 departments who work together to develop novel anticancer therapies and translate these therapies into the clinic. This productive program has total annual external cancer-related funding of $8.5M ($5.9M annual direct costs, of which 28% is from the NCI). Members published 366 publications over the current funding period, 99 (27%) of which are inter-programmatic, 84 (23%) are intra-programmatic, and 189 (52%) are inter-institutional. The DT program Co-leaders, Drs. Jill Kolesar and Jon Thorson, have a long-standing collaboration and bring complementary expertise in biomarker discovery, drug development, and early clinical trials. Both direct key resources supporting the DT program, the MCC Precision Medicine Center and the UK Center for Pharmaceutical Innovation, respectively. Each leader brings critical strengths including local, national and international collaborations, entrepreneurial relationships, and active participation in NCI initiatives. Taken together, the DT program has a cohesive and collaborative team that translates novel biomarkers into targets for effective anticancer treatments.

项目概要/摘要马基癌症中心的药物发现、递送和转化治疗 (DT) 项目 (MCC) 科学地专注于识别新靶标和生物标志物以及发现和开发针对这些生物标志物的新药。 MCC 流域人口具有较高的癌症风险与过度接触致癌物以及由于地理因素而无法获得尖端临床试验有关孤立和贫困的社会经济地位。 DT 计划的愿景是了解独特的分子和肯塔基州癌症的表型标志物以及获得护理和整合这些知识的障碍为药物发现、开发和交付早期临床试验工作提供信息，以应对难以达到的目标阿巴拉契亚肯塔基州人口。 MCC 研究人员是生物标志物发现领域的国际领导者（主题 1) 正在进行包括 600 多名参与者在内的转化研究，评估环境的作用致癌物和鉴定肺癌的生物标志物。 DT 制药科学家致力于发现和开发针对已识别突变和表型的新抗癌药物（主题 2），与癌细胞生物学和信号转导 (CS) 以及基因组不稳定性、表观遗传学和代谢 (GEM) 项目成员。例如，一种新型的 4E-BP1 磷酸化调节剂（一种经过验证的结肠癌靶点）是从阿巴拉契亚天然产物资源库中鉴定出。 DT 研究人员领导临床试验，重点关注与该地区相关的癌症（主题 3），已招募了 500 多名肺癌、结肠癌和癌症患者卵巢介入治疗和诊断试验。他们定期与癌症预防和 Control (CP)、CS 和 GEM 计划成员为 MCC 基础科学提供信息和推进，例如，将 PAR-4 在 CS 中的抗癌活性的早期鉴定转化为针对 PAR-4 的临床试验保密者。 DT 是一个跨学科项目，由来自 6 个学院和 18 个系的 47 名研究人员组成。共同开发新型抗癌疗法并将这些疗法转化为临床。这富有成效的计划每年与癌症相关的外部资金总额为 850 万美元（每年直接成本为 590 万美元）其中 28% 来自 NCI）。成员在当前资助期内发表了 366 篇出版物，其中 99 篇（27%）其中 84 个 (23%) 是项目内的，189 个 (52%) 是机构间的。 DT 项目联合领导者，博士。 Jill Kolesar 和 Jon Thorson 有着长期的合作并带来了生物标志物发现、药物开发和早期临床试验方面的互补专业知识。都是直接键支持 DT 项目、MCC 精准医学中心和英国中心的资源分别是制药创新。每位领导者都具有关键优势，包括地方、国家和国际合作、企业关系以及积极参与 NCI 倡议。采取 DT 项目拥有一支富有凝聚力和协作精神的团队，可将新型生物标志物转化为靶标以获得有效的抗癌治疗。