Clinical and Translational Oncology Program (CTOP)

临床与翻译肿瘤学文摘：摘要 临床和转化肿瘤学计划（CTOP）的总体目标是将基本和 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，以预防，诊断和治疗癌症的集水区， 超越。CTOP是一个重新设计的计划，从长期的治疗发展中出现。 程序.经过严格的审查和新的成像重点成员的增加， 将其重点从药物开发扩展到全方位的转化和临床研究， 患有癌症的人类受试者CTOP围绕三个具体目标构建：（1）发现和优化新的 用于治疗转化的药物、生物标志物和成像方式;（2）开发机制研究者- 翻译或反向翻译的启动试验（IIT）;（3）进行临床试验，测试 新的或改变用途的疗法。在过去的资助期内，代理发现和优化方面取得了重大进展 包括FDA批准阿法黑肽用于保护皮肤免受阳光诱导的紫外线诱变， 用于阻断肿瘤中的自噬和铁获得的新化合物， 调节致癌信号传导，并鉴定非成瘾性先导化合物， 尤其是癌症或其治疗引起的疼痛。CTOP成员已经建立了一个强大的IIT管道， 包括用于机械翻译的机会窗口和整体生物标志物设计。于本 5-在一年的资助期内，CTOP招募了2，534名患者参加临床试验，其中1，167名患者接受了介入治疗 试验（233项IIT），与前一时期相比增加了6.8倍。高影响力的IIT包括 在急性髓性白血病（AML）中评价一类NAE抑制剂pevonedistat;重新利用 苯达莫司汀用于预防单倍相合骨髓移植中的移植物抗宿主病， 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），在头颈癌中的应用;以及 屈大麻酚治疗阿片类药物依赖性骨转移性乳腺癌CTOP的52名成员有一个同行评审 490万美元（直接成本）的资金基础，其中220万美元（45%）来自国家癌症研究所，260万美元（53%）来自 来自其他国立卫生研究院的资金，以及来自其他同行评审来源的10万美元（2%）， 这意味着同行评审资金增加了17%。CTOP成员共获得35项MPI赠款， 2350万美元的癌症相关直接成本。这些MPI包括14架R 01、2架P01、1架U 54和合作伙伴 全国有28个机构，其中四个是NCI指定的癌症中心。自2016年以来， 成员撰写了386篇癌症相关出版物，其中75篇（19%）是计划内的，78篇（20%）是计划内的。 203项（53%）是跨方案的，203项（53%）是跨机构的。此外，CTOP成员提交了116项专利， 其中17个（15%）已发出。

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.