Molecular Medicine

项目总结 分子医学计划 分子医学(MM)计划的首要目标是将系统生物学、药物发现、 和精准医学方法，以开发、验证和交付新的治疗策略和试剂，以及 推动具有里程碑意义的试验，改善我们集水区和其他地区患者的护理标准。钥匙 MM的首要任务是：1)识别和验证致癌回路的关键效应物和生物标记物 进展、转移和治疗耐药；2)开发新的分子探针，将促进机制 了解优先靶点在肿瘤发生中的作用；3)优化靶向制剂的类药物特性 通过药物化学在临床试验中进行测试；以及4)进行有效的临床试验，从而导致 护理标准的变化。为了实现这些目标，MM研究被组织成三个具体目标： 目的1：确定和验证肿瘤转移和治疗抵抗的途径和靶点。 目的2：确定作用机制，优化现有药物和先导化合物。 目的3：用精确医学方法设计和实施治疗试验。 MM由55名基础和临床研究人员组成，他们组成了多学科团队，创造了独特的 转化型研究的机会主要集中在从床到床的医学。此外，在前馈中 时下，来自临床试验的发现为重要的新研究提供信息，以完善策略和 靶向药物，并开发诊断、预后和反应的预测性生物标志物。这个强健的循环 MM计划招募了12名新成员，推动了研究和试验的流水线， 拥有15名助理、15名助理和25名高级成员的健康平衡，以及投资 在解决莫菲特办公室确定的具体目标和关键集水区优先事项的关键目标领域 社区外展、参与和公平。MM计划目前拥有3520万美元的总资金， 包括890万美元的同行评审资金和2630万美元的非同行评审资金。MM成员已公布 1 302篇文章，其中323篇(25%)为方案内出版物，412篇(32%)为方案间出版物； 具有272件高影响物品(影响系数&10)。重要的是，多发性骨髓瘤使3926名患者进入介入临床 审判，包括2,333项由调查员发起的审判。值得注意的是，MM对黑色素瘤、肺癌和 老年患者的癌症对我们的癌症负担和高危人群产生了重大影响 集水区和重要的MM临床试验导致了FDA的批准和国家 全面癌症网络(NCCN)指南。MM计划未来的优先事项是：1)结合 用化学和蛋白质组学无偏见的细胞表型筛选同时识别靶标和 化学先导；2)完全整合整体和单细胞组学分析，以提供机制和靶点；3)应用 机器学习为精准医学提供动力；4)招募内科科学家支持孢子和P01倡议； 以及5)在优先人群中扩大集水区的新疗法。

PROJECT SUMMARY MOLECULAR MEDICINE PROGRAM The overarching goal of the Molecular Medicine (MM) Program is to integrate systems biology, drug discovery, and precision medicine approaches to develop, validate and deliver new therapeutic strategies and agents, and to drive landmark trials that improve standard-of-care for patients in our catchment area and beyond. Key priorities of MM are to: 1) identify and validate key effectors and biomarkers of circuits that drive cancer progression, metastasis, and therapy resistance; 2) develop new molecular probes that will facilitate mechanistic understanding of the roles of priority targets in tumorigenesis; 3) optimize drug-like properties of targeted agents through medicinal chemistry, for testing in clinical trials; and 4) conduct impactful clinical trials that lead to changes in standard of care. To accomplish these goals, MM research is organized into three Specific Aims: Aim 1: To identify and validate pathways and targets of cancer metastases and therapy resistance. Aim 2: To define mechanisms of action and optimize existing drugs and lead compounds. Aim 3: To design and implement therapeutic trials with a precision medicine approach. MM is comprised of 55 basic and clinical researchers who have formed multidisciplinary teams that create unique opportunities for translational research focused on bench-to-bedside medicine. Further, in a feed-forward fashion, findings coming from clinical trials inform important new research at the bench, to refine strategies and targeted agents, and to develop predictive biomarkers of diagnosis, prognosis, and response. This robust cyclic pipeline of research and trials has been driven by the recruitment of twelve new Members to the MM Program, which has a healthy balance of 15 Assistant, 15 Associate, and 25 Senior Members, as well as by investments in key target areas that address the Specific Aims and key catchment area priorities identified by Moffitt’s Office of Community Outreach, Engagement, and Equity. The MM Program currently holds $35.2 M in total funding, including $8.9M in peer-reviewed funding and $26.3M in non-peer-reviewed funding. MM members published 1,302 articles, with 323 (25%) intra-programmatic publications, 412 (32%) inter-programmatic publications, and with 272 high impact articles (impact factor >10). Importantly, MM accrued 3,926 patients to interventional clinical trials, including 2,333 to investigator-initiated trials. Notably, MM research on melanoma, lung cancer, and cancers in elderly patients have made a significant impact on the cancer burden and at-risk populations in our catchment area and, importantly, MM clinical trials have resulted in FDA approvals and changes in National Comprehensive Cancer Network (NCCN) guidelines. Future priorities of the MM Program are to: 1) combine unbiased cell-based phenotypic screening with chemistry and proteomics to simultaneously identify target and chemical leads; 2) fully integrate bulk and single cell ‘omics analyses to inform mechanisms and targets; 3) apply machine learning to fuel precision medicine; 4) recruit physician scientists to support SPORE and P01 initiatives; and 5) expand novel treatments in the catchment area among priority populations.