Clinical and Translational Oncology Program (CTOP)

临床和转化肿瘤学项目 (CTOP)

基本信息

批准号：
10493908
负责人：
Julie E Bauman
金额：
$ 7.36万
依托单位：
UNIVERSITY OF ARIZONA
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：
1997-07-01 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10493908
关键词：
Acute Myelocytic Leukemia Animal Model Arizona Autophagocytosis Award Biochemistry Biological Markers Bone Marrow Transplantation Cancer Burden Cancer Center Cancer Center Support Grant Catchment Area Cell model Chemoprevention Clinic Clinical Clinical Oncology Clinical Research Clinical Trials Clinical Trials Design Collaborations Conduct Clinical Trials Country Detection Development Diagnosis Direct Costs Disease Doctor of Philosophy Dronabinol Drug Targeting Engineering Enrollment Evaluation FDA approved Funding Glioblastoma Goals Grant Head and Neck Cancer Human Image Institution Intervention Investigation Iron Laboratories Lead Legal patent Malignant Neoplasms Medical Oncologist Metastatic breast cancer Mission Monoclonal Antibodies NCI-Designated Cancer Center National Cancer Institute New Agents Nitric Oxide Oncogenic Opiate Addiction Pain management Patients Peer Review Population Program Development Publications Radiation therapy Scientist Signal Transduction Skin Source Structure Systemic Therapy The Sun Therapeutic Tissues Translating Translational Research Translations UV Mutagenesis UV induced United States National Institutes of Health Universities afamelanotide arm base biomarker-driven bone cancer imaging cancer therapy clinical application clinical development clinical efficacy clinical translation design drug development drug discovery efficacy testing functional genomics graft vs host disease human subject imaging approach imaging biomarker imaging modality inhibitor innovation instrumentation inter-institutional investigator-initiated trial lead optimization member new therapeutic target novel oncology program prevent programs therapeutic development translational clinical trial translational oncology translational pipeline translational scientist treatment trial tumor working group

项目摘要

CLINICAL & TRANSLATIONAL ONCOLOGY PROGRAM: ABSTRACT The overarching goal of the Clinical & Translational Oncology Program (CTOP) is to bring together basic and clinical scientists to transform scientific discoveries into clinical applications in pursuit of the broader University of Arizona Cancer Center (UACC) mission to prevent, diagnose, and treat cancer in the Catchment Area and beyond. CTOP is a redesigned program that emerged from the long-standing Therapeutic Development Program. After rigorous review and addition of new imaging-focused members, the renamed Program expanded its focus from drug development to the full spectrum of translational and clinical research involving human subjects with cancer. CTOP is structured around three Specific Aims: (1) discover and optimize new agents, biomarkers, and imaging modalities for therapeutic translation; (2) develop mechanistic investigator- initiated trials (IITs) for translation or reverse translation; and (3) conduct clinical trials testing the efficacy of new or repurposed therapies. Critical advances in agent discovery and optimization in the past funding period include the FDA approval of afamelanotide for protection of skin from sun-induced UV mutagenesis, discovery of novel compounds for blocking autophagy and iron acquisition in tumors, discovery of numerous compounds that modulate oncogenic signaling, and identification of non-addictive lead compounds for the management of pain specifically from cancer or its treatment. CTOP Members have established a robust pipeline of IITs, including window-of-opportunity and integral biomarker designs, for mechanistic translation. During the current 5-year funding period, CTOP enrolled 2,534 patients to clinical trials including 1,167 to interventional treatment trials (233 IITs), representing a 6.8 fold increase compared to the prior period. High-impact IITs include those evaluating first-in-class NAE inhibitor pevonedistat in Acute Myeloid Leukemia (AML); repurposing bendamustine for preventing graft-vs-host disease in haplo-identical bone marrow transplant, of importance for UACC’s Catchment Area population; evaluating NVX-108 to enhance radiotherapy for glioblastoma multiforme; evaluating ficlatuzumab, an anti-HGF monoclonal antibody (mAb), in head and neck cancer; and evaluating dronabinol for opioid-dependent, bone-metastatic breast cancer. CTOP’s 52 Members have a peer-reviewed funding base of $4.9M (direct costs) of which $2.2M (45%) is from the National Cancer Institute, $2.6M (53%) from other National Institutes of Health sources, and $0.1M (2%) from other peer-reviewed sources, representing a 17% increase in peer-reviewed funding. CTOP Members were awarded 35 MPI grants totaling $23.5M in cancer-relevant direct costs. These MPIs included 14 R01s, two P01s, one U54s, and partnerships with 28 institutions across the country, of which four were NCI-designated cancer centers. Since 2016, Members authored 386 cancer-relevant publications, of which 75 (19%) were intraprogrammatic, 78 (20%) were interprogrammatic, and 203 (53%) were inter-institutional. In addition, CTOP Members filed 116 patents, of which 17 (15%) were issued.

临床与转化肿瘤学项目：摘要临床与转化肿瘤学计划 (CTOP) 的总体目标是将基础和转化结合起来临床科学家将科学发现转化为临床应用，以追求更广泛的大学亚利桑那州癌症中心 (UACC) 的使命是在集水区预防、诊断和治疗癌症， Beyond 是一项重新设计的计划，源自长期的治疗开发。经过严格审查并增加新的以成像为重点的成员后，更名为该计划。其重点从药物开发扩展到全方位的转化和临床研究，涉及 CTOP 围绕三个具体目标构建：(1) 发现和优化新的癌症。 (2) 发展机械研究者- 启动翻译或反向翻译试验（IIT）；以及（3）进行临床试验来测试其功效新的或重新利用的疗法在过去的资助期间发现和优化的关键进展。包括 FDA 批准阿法诺肽用于保护皮肤免受阳光诱导的紫外线诱变，发现用于阻断肿瘤自噬和铁获取的新型化合物，发现了多种化合物调节致癌信号，并鉴定用于管理的非成瘾先导化合物特别是来自癌症或其治疗的疼痛 CTOP 成员已经建立了强大的 IIT 管道，包括机会之窗和整体生物标志物设计，用于当前的机械翻译。 5年资助期内，CTOP招募了2,534名患者参加临床试验，其中1,167名患者接受介入治疗试验（233 个 IIT），比上一期增加了 6.8 倍高影响力 IIT 包括这些。评估一流的 NAE 抑制剂 pevonedistat 在急性髓系白血病 (AML) 中的再利用；苯达莫司汀用于预防单倍体骨髓移植中的移植物抗宿主病，对于 UACC 的集水区人群；评估 NVX-108 增强多形性胶质母细胞瘤的放射治疗；评估 ficlatuzumab（一种抗 HGF 单克隆抗体 (mAb)）在头颈癌中的作用；屈大麻酚用于治疗阿片类药物依赖性骨转移性乳腺癌，CTOP 的 52 名成员已接受同行评审。资金基础为 490 万美元（直接成本），其中 220 万美元（45%）来自国家癌症研究所，260 万美元（53%）来自其他国立卫生研究院来源，以及来自其他同行评审来源的 10 万美元 (2%)，同行评审资金增加了 17%，CTOP 成员总共获得了 35 项 MPI 资助。这些 MPI 包括 14 个 R01、2 个 P01、1 个 U54 和合作伙伴关系，费用为 2,350 万美元。自 2016 年以来，在全国设有 28 个机构，其中 4 个是 NCI 指定的癌症中心。成员撰写了 386 篇癌症相关出版物，其中 75 篇 (19%) 为程序内出版物，78 篇 (20%) 是跨计划的，203 项（53%）是跨机构的。此外，CTOP 成员申请了 116 项专利，其中 17 份（15%）已发行。