Drug Discovery, Delivery, and Translational Therapeutics Research Program

药物发现、递送和转化治疗研究计划

• 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
• 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

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.

项目摘要/摘要 Markey癌症中心的药物发现、交付和转译治疗(DT)计划 (MCC)科学地专注于识别新的靶点和生物标志物，并发现和开发 针对这些生物标志物的新药。MCC集水区的人口既有很高的癌症风险 与过量接触致癌物有关，以及由于地理原因而无法获得尖端临床试验 与世隔绝，社会经济地位低下。DT计划的愿景是理解独特的分子和 肯塔基州癌症的表型标志物以及获得护理和整合这一知识的障碍 为药物发现、开发和早期临床试验的交付提供信息，以实现难以实现的目标 阿巴拉契亚肯塔基州人口。MCC调查人员是发现生物标记物的国际领导者(主题 1)正在进行的包括600多名参与者的翻译研究，评估环境的作用 致癌物质和识别肺癌的生物标志物。DT制药科学家致力于发现和 开发针对已识别的突变和表型的新抗癌药物(主题2)，与 癌细胞生物学和信号(CS)与基因组不稳定性、表观遗传学和代谢(GEM)计划 会员。例如，一种新的4E-BP1磷酸化调节剂，一个有效的结肠癌靶点，是 从阿巴拉契亚天然产品储存库中鉴定出来。DT研究人员领导临床试验，重点是 与集水区相关的癌症(主题3)，并招募了500多名肺癌、结肠癌和 卵巢介入治疗和诊断试验。他们定期与癌症预防和 控制(CP)、CS和GEM计划成员，以告知和推进MCC基础科学，例如， 将CS中PAR-4抗癌活性的早期鉴定转化为以PAR-4为重点的临床试验 监管者。DT是一个由来自6所学院和18个系的47名研究人员组成的跨学科项目，他们 共同开发新的抗癌疗法，并将这些疗法转化为临床。这 Productive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)。成员在当前资助期间出版了366份出版物，其中99份(27%) 其中84个(23%)是计划内的，189个(52%)是机构间的。《DT》 项目联合负责人Jill Kolesar博士和Jon Thorson博士长期合作，并带来了 在生物标记物发现、药物开发和早期临床试验方面的互补专业知识。两个都是直接键 支持DT计划的资源、MCC精密医学中心和英国中心 分别是医药创新。每个领导者都带来了关键的优势，包括地方、国家和 国际合作、企业关系和积极参与NCI计划。已被占用 总而言之，DT计划拥有一个具有凝聚力和协作性的团队，将新的生物标记物转化为靶标 用于有效的抗癌治疗。