Cancer Pharmacology

癌症药理学

基本信息

批准号：
10357813
负责人：
STEVEN ZHENG
金额：
$ 1.98万
依托单位：
RBHS -CANCER INSTITUTE OF NEW JERSEY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10357813
关键词：
Absence of pain sensation Address Amino Acids Antineoplastic Agents Antioxidants Back Basic Science Biology Biomedical Engineering Body mass index Cancer Center Cancer Center Support Grant Cancer Detection Cancer Institute of New Jersey Cancer Patient Cardiac Cardiotoxicity Cells Cellular Metabolic Process Chemicals Childhood Glioblastoma Clinic Clinical Trials Colorectal Cancer Communication Development Dose-Limiting Drug Delivery Systems Drug Targeting Drug resistance Enhancers FRAP1 gene Failure Feedback Funding GRM1 gene Goals Growth Image Institution Journals Knowledge Malignant Neoplasms Medicine Methods Modality Molecular Molecular Analysis Molecular Biology Molecular Target Nature New Jersey Nucleic Acids Paper Pathway interactions Patient-Focused Outcomes Peer Review Grants Peptide antibodies Pharmaceutical Chemistry Pharmacology Pharmacy (field)Precision therapeutics Prodrugs Protocols documentation Publications Publishing Rare Earth Metals Regulation Research Research Personnel Resource Sharing Resources Riluzole Schools Science Signal Transduction Sirolimus TP53 gene Technology Therapeutic Topoisomerase Toxin Translating Translational Research Universities Work base bench to bedside cancer care cancer cell cancer pharmacology cancer therapy cell growth chemotherapeutic agent childhood sarcoma chronic pain management clinical application clinical investigation drug development drug discovery epigenetic regulation improved inhibitor innovation insight inter-institutional manganese oxide melanoma member mutant nanocarrier novel novel anticancer drug novel therapeutics pre-clinical research programs resistance mechanism sarcoma side effect small molecule stem targeted cancer therapy technology development thionicotinamide translational pipeline treatment response tumor

项目摘要

CANCER PHARMACOLOGY PROGRAM PROJECT SUMMARY/ABSTRACT The Cancer Pharmacology (CP) Program has the overall goal to discover and develop more effective cancer treatments through pharmacology-based preclinical research. The ultimate aim is to improve patient outcomes through innovative and integrative research in cancer target biology, chemical biology, medicinal chemistry, pharmaceutics and biomedical engineering. Defining molecular functions of cancer targets and leveraging this knowledge to drive translational bench-to-bedside and bedside-to-bench research in drug discovery and delivery are signature Program features that span the Rutgers/Princeton Consortium. CP provide a platform for productive, collaborative and impactful science and discoveries. CP has 37 members from 18 Departments, 7 Schools, 2 Universities. The Program is well funded with $16.5M annual direct peer-reviewed grant support, $6.1M of which is cancer-focused (13 R01 equivalent, and 6 Multi-PI). CP members published 746 papers (up from 522 in 2004-10), 29% of which are collaborative (18% intra- and 18% inter-programmatic) with 22% in top-tier journals and 53% collaborative with other institutions. This represents an increase in both total and collaborative publications compared with last project period. Impactful science includes regulation of growth pathways by GRM1 in melanoma, novel mechanisms of amino acid signaling by mTOR in colorectal cancer, and epigenetic regulation in pediatric glioblastomas/sarcomas. CP members revealed key roles of mTOR and antioxidant pathways in cardiac protection and chronic pain management, which have implications for reducing cardiac toxicity, a dose-limiting side effect of chemo-therapy, and for improving analgesia in advanced stage cancer patients. Based on fundamental insights into the biology of molecular targets, CP members determined the mode of action for riluzole (a repurposed ALS drug) targeting GRM1 in melanoma and identified determining factors for therapeutic response for rapamycin. CP members focused on development of novel therapeutics and drug delivery technologies, and identified novel anticancer agents including a compound that restores mutant p53 function, BMI-1 inhibitors, and prodrugs for riluzole and the CINJ-developed topoisomerase 1 inhibitor Genz-644282. They developed innovative tumor-targeting nanocarriers containig multiple therapeutic modalities (small molecules, toxins, nucleic acids, and peptides/antibodies) and imaging enhancers (e.g., rare earth elements and Mn3O4), enabling cancer detection and treatment. CP members work with other CINJ Programs, particularly the Clinical Investigations and Precision Therapeutics Program (CIPT), to translate bench discoveries to clinical trials, contributing significantly to CINJ’s translational pipeline. They also use feedback from trials to gain further insight into target biology and mechanisms of treatment response for agents such as riluzole to improve therapeutic approaches.

癌症药理学项目项目概要/摘要癌症药理学（CP）计划的总体目标是发现和开发更有效的癌症通过基于药理学的临床前研究进行治疗的最终目的是改善患者的治疗结果。通过癌症靶标生物学、化学生物学、药物化学的创新和综合研究，药剂学和生物医学工程。定义癌症靶点的分子功能并利用它。推动药物发现和临床研究转化的知识罗格斯大学/普林斯顿大学联盟的标志性项目功能提供了一个平台。 CP 拥有来自 18 个部门、7 个部门的 37 名成员。学校、2 所大学该计划资金充足，每年提供 1650 万美元的直接同行评审赠款支持，其中 610 万美元用于癌症研究（13 名 R01 同等金额和 6 名 Multi-PI 成员发表了 746 篇论文）。（2004-10 年为 522 个），其中 29% 是与 22% 发表在顶级期刊上，53% 发表在与其他机构的合作上，这表明两者均有所增加。与上一个项目期间相比，有影响力的科学包括监管。 GRM1 对黑色素瘤生长途径的影响，mTOR 在结直肠中氨基酸信号传导的新机制癌症和儿童胶质母细胞瘤/肉瘤中的表观遗传调控揭示了 CP 成员的关键作用。 mTOR 和抗氧化途径在心脏保护和慢性疼痛管理中的意义用于减少心脏毒性（化疗的剂量限制副作用）以及改善镇痛作用基于对分子靶标生物学的基本见解，CP。成员确定了利鲁唑（一种重新利用的 ALS 药物）针对黑色素瘤中 GRM1 的作用方式并确定了雷帕霉素治疗反应的决定因素。开发治疗小说和药物输送技术，并确定新型抗癌药物包括恢复突变型 p53 功能的化合物、BMI-1 抑制剂以及利鲁唑和 CINJ 开发的拓扑异构酶 1 抑制剂 Genz-644282 他们开发了创新的肿瘤靶向药物。纳米载体含有多种治疗方式（小分子、毒素、核酸和肽/抗体）和成像增强剂（例如稀土元素和 Mn3O4），从而实现癌症检测 CP 成员与其他 CINJ 项目合作，特别是临床研究和治疗。精准治疗计划 (CIPT)，将实验室发现转化为临床试验，有助于他们还利用试验反馈来深入了解目标。利鲁唑等药物的生物学和治疗反应机制，以改善治疗方法。