Translational Oncology Research Program

项目总结/摘要 Markey癌症中心（MCC）的转化肿瘤学（TO）研究计划科学地 专注于确定新的目标，发现新的抗癌药物和设备，并领导集水- 相关的临床试验，以减少癌症负担在肯塔基州和国家。TO的首要主题 该计划是通过三个具体目标使用精准医学来提高患者的治疗效果：1）识别和 验证癌症的机制靶点，2）发现，重新设计和开发新的抗癌药物和设备， 和3）开发和领导生物标志物导向的，与流域相关的临床试验。目前，33个正在进行中 翻译研究正在评估癌症的分子靶标和介质。自2018年以来，38种新药， 已经开发了新的组合和再利用的抗癌剂和装置，重点是 根据COE集水区数据确定的突变和表型。TO是一个跨学科的 来自四所学院和16个部门的67名研究人员参加了该计划， 每年直接成本约为1000万美元，比2017年增长68%，其中包括来自NCI的180万美元， 其他NIH机构的340万美元。会员共发表稿件613篇（2018 - 2022），其中148篇 (24 169个（28%）是方案间的，344个（56%）是机构间的，13%的 影响因子>10。TO成员领导26个新的治疗性介入治疗发起 试验（IIT），自上一个资助期（17个IIT，2013-2017）以来增加了53%。这些IIT已经注册了 870例患者（2018-2022年），IIT应计费用增加111%（413例患者，2013-2017年），参与者占52% 来自阿巴拉契亚。此外，TO研究人员招募了12，689名参与该项目的干预和 非干预性试验，与2013-2017年的8，571项相比，增加了48%。TO计划成员包括 目标发现和验证方面的国际领导者，拥有国家和国际合作， 在国家癌症研究所的实验治疗药物临床试验网络中担任领导角色， 肿瘤学研究信息交换网络和肿瘤阵列网络，以及MCC领导的全球 癌症联盟。TO计划促进MCC计划成员之间的持续合作， 告知并推进MCC基础科学进入临床。例子包括翻译早期识别的 一项正在进行的结直肠癌试验，并证明了肿瘤抑制因子的上调， PAR-4的羟氯喹在三个试验。TO计划有一个专注于团结协作的团队 将MCC的科学发现转化为安全有效的抗癌治疗， MCC在国内和国际上对集水区影响的深度和广度。

PROJECT SUMMARY/ABSTRACT The Markey Cancer Center’s (MCC) Translational Oncology (TO) Research Program is scientifically focused on identifying novel targets, discovering new anticancer agents and devices, and leading catchment- relevant clinical trials to decrease cancer burden in Kentucky and the nation. The overarching theme of the TO Program is to use precision medicine to enhance patient outcomes through three Specific Aims: 1) Identify and validate mechanistic targets of cancer, 2) Discover, re-design and develop new anticancer agents and devices, and 3) Develop and lead biomarker directed, catchment-relevant clinical trials. Currently, 33 ongoing translational studies are evaluating molecular targets and mediators of cancer. Since 2018, 38 new drugs, novel combinations and repurposed anticancer agents and devices have been developed, with a focus on identified mutations and phenotypes as informed by COE catchment area data. TO is a cross-disciplinary program with 67 investigators from four colleges and 16 departments producing research awards of approximately $10M in annual direct costs, a 68% increase from 2017, including $1.8M from the NCI and $3.4M from other NIH agencies. Members have published 613 manuscripts (2018 to 2022), of which 148 (24%) are inter-programmatic, 169 (28%) are intra-programmatic, 344 (56%) are inter-institutional, and 13% of which have an impact factor >10. TO members lead 26 new therapeutic interventional investigator-initiated trials (IITs), a 53% increase since the previous funding period (17 IITs, 2013-2017). These IITs have enrolled 870 patients (2018-2022), a 111% increase in IIT accruals (413 patients, 2013-2017), with 52% of participants from Appalachia. In addition, TO investigators enrolled 12,689 individuals to the program’s interventional and non-interventional trials, compared to 8,571 from 2013-2017, a 48% increase. TO Program members are international leaders in target discovery and validation, have national and international collaborations and hold leadership roles in the National Cancer Institute’s Experimental Therapeutics Clinical Trials Network, the Oncology Research Information Exchange Network and Onco-Array Networks, and the MCC-led Global Cancer Consortium. The TO Program fosters continuous collaboration among MCC program members to inform and advance MCC basic science into the clinic. Examples include translating early identification of the biomarker FASN to an ongoing colorectal cancer trial and demonstrating the upregulation of tumor suppressor PAR-4 by hydroxychloroquine in three trials. The TO Program has a cohesive and collaborative team focused on translating MCC scientific discoveries into safe and effective anticancer treatments with a demonstrated depth and breadth of impact in MCC’s catchment area, nationally and internationally.