Program 3: Free Radical Metabolism and Imaging

在过去的二十年里，大量的证据表明新陈代谢 氧化/还原反应是促进和促进 恶性肿瘤的进展，以及选择性地使癌细胞对治疗敏感的治疗靶点 干预措施。与此同时，人们认识到先进的医学成像技术， 在治疗前和治疗期间测量癌症组织与正常组织的代谢变化显示出很大的希望 在允许对癌细胞代谢的基本差异进行非侵入性量化和监测方面 提高癌症治疗水平。自由基代谢和成像(FRMI)计划(32名正式成员和9名成员 代表3个学院和10个系的准成员)于2014年由以前的 自由基癌生物学和肿瘤成像计划充分利用 这两个学科的科学。 FRMI计划有四个研究主题：1)自由基癌症生物学，基础研究 癌症生物学中氧化还原生化的差异及其对细胞信号、遗传学和表观遗传学的影响 和治疗；2)基于氧化还原的治疗，开发和测试基于 利用自由基代谢的根本差异选择性清除癌细胞 保护正常组织；3)患者预后和分子成像，新图像的发展- 在癌症治疗中使用分子增强和预测患者预后的指导治疗方法 和代谢成像技术；以及4)诊断成像的新方法，开发新的 将最先进的功能和解剖成像技术集成到癌症生物学和 心理治疗。 FRMI成员在上一次支持期间高度合作，总共有250名癌症相关患者 出版物(2011-2015)，其中53%(n=133)涉及2名或2名以上成员之间的合作 Hccc。在合作出版物中，66%(n=88)是方案内出版物，60%(n=81)是方案间出版物 程序化的。此外，30%(n=76)是跨机构的，与计划成员共同编写45 与美国其他癌症中心的教职员工一起出版。十篇手稿 在高影响力期刊上发表(影响因子≥10)。该计划的成员得到了5857,820美元的支持 经同行审查的资金总额和去年CCSG支助的NCI资金2,699,266美元。成功者 完成fRMI推行的研究计划将涉及临床前和临床验证 靶向肿瘤细胞氧化代谢过程的范式转换方法 提高治疗效果，并实施新的基于图像的预测方法 临床结果、监测反应和指导决策。

During the past two decades a significant body of evidence has accumulated showing that metabolic oxidation/reduction reactions represent a significant underlying mechanism contributing to promotion and progression of malignancy, as well as a therapeutic target for selectively sensitizing cancer cells to therapeutic interventions. Evolving in parallel has been the recognition that advanced medical imaging techniques, measuring metabolic changes in cancer versus normal tissues before and during therapy show great promise in allowing non-invasive quantitation and monitoring of fundamental differences in cancer cell metabolism to improve cancer therapy. The Free Radical Metabolism and Imaging (FRMI) Program (32 full members and 9 associate members) representing 3 colleges and 10 departments was formed by a merger in 2014 of former programs in Free Radical Cancer Biology and Tumor Imaging to take full advantage of the convergence of the science in these two disciplines. The FRMI program has four research themes: 1) Free Radical Cancer Biology, the study of fundamental differences in redox biochemistry and its impact on cell signaling, genetics and epigenetics in cancer biology and therapy; 2) Redox-Based Therapeutics, the development and testing of novel cancer therapeutics based on exploiting fundamental differences in free radical metabolism to selectively eradicate cancer cells while protecting normal tissues; 3) Patient Outcomes and Molecular Imaging, the development of novel image- guided therapy approaches for enhancing and predicting patient outcomes in cancer therapy using molecular and metabolic imaging techniques; and 4) Novel Approaches to Diagnostic Imaging, the development of novel approaches that integrate state-of-the-art functional and anatomic imaging techniques into cancer biology and therapy. FRMI members were highly collaborative during the last period of support with a total of 250 cancer relevant publications (2011-2015) including 53% (n=133) involving collaborations between 2 or more members of the HCCC. Of the collaborative publications, 66% (n=88) were intra-programmatic and 60% (n=81) were inter- programmatic. In addition, 30% (n=76) were interinstitutional with members of the program co-authoring 45 publications with faculty members at other cancer centers in the United States. Ten manuscripts were published in high impact journals (impact factor ≥10). The program members were supported by $5,857,820 of total peer-reviewed funding and $2,699,266 of NCI funding in the last year of CCSG support. The successful completion of the research initiatives pursued by FRMI would involve preclinical and clinical verification of a paradigm shifting approach for targeting oxidative metabolic processes in cancer cells as indicated by selective enhancement of therapeutic outcomes, and implementation of new image-based approaches to predicting clinical outcomes, monitoring response and guiding decision-making.