Clinical and Translational Oncology Program (CTOP)

临床与转译肿瘤学计划：摘要 临床和转化性肿瘤学计划(CTOP)的首要目标是将基础和 临床科学家将把科学发现转化为临床应用，追求更广阔的大学 亚利桑那州癌症中心(UACC)在集水区预防、诊断和治疗癌症的使命 更远一点。CTOP是一个重新设计的计划，它是从长期的治疗开发中出现的 程序。在严格审查和添加新的专注于成像的成员后，更名的计划 将其重点从药物开发扩展到全方位的翻译和临床研究，包括 患有癌症的人类研究对象。CTOP围绕三个具体目标构建：(1)发现和优化新的 用于治疗性翻译的试剂、生物标志物和成像方式；(2)开发机械调查员- 翻译或反向翻译的启动试验(IITs)；以及(3)进行临床试验，测试 新的或重新调整用途的疗法。过去资助期在代理发现和优化方面取得的重大进展 包括FDA批准阿霉胺用于保护皮肤免受阳光诱导的紫外线诱变，发现 在肿瘤中发现了许多用于阻断自噬和铁获取的新化合物 调节致癌信号，并鉴定用于管理的非成瘾先导化合物 疼痛，特别是癌症或其治疗引起的疼痛。CTOP成员已经建立了一条强大的信息和通信技术管道， 包括机会之窗和整体生物标记设计，用于机械翻译。在当前的 在5年的资助期内，CTOP招募了2,534名患者进行临床试验，其中1,167名接受介入治疗 审判(233个机构间信托基金)，与上一期间相比增加6.8倍。影响较大的综合投资信托基金包括 评估一类NAE抑制剂pevonedexat在急性髓系白血病(AML)中的应用；改变用途 苯达莫司汀用于预防单倍体相合骨髓移植中移植物抗宿主病，对 UACC集水区人群；评价NVX-108增强放射治疗多形性胶质母细胞瘤； 评估抗肝细胞生长因子单抗(MAb)在头颈癌中的应用 屈诺比诺治疗阿片依赖型骨转移乳腺癌。CTOP的52名成员有同行评议 资助基数为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%) 来自其他国家卫生研究院的资金，以及来自其他同行审查来源的10万美元(2%)， 这意味着同行审查资金增加了17%。CTOP成员获得了35项MPI奖助金，总计 2350万美元，与癌症相关的直接成本。这些MPI包括14个R01、两个P01、一个U54和合作伙伴 在全国有28个机构，其中4个是NCI指定的癌症中心。自2016年以来， 成员撰写了386份癌症相关出版物，其中75份(19%)是计划内出版物，78份(20%)是计划内出版物 是跨方案的，203个(53%)是跨机构的。此外，CTOP成员还提交了116项专利， 其中17张(15%)已发行。

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.