Monitoring the interactions between cancer cell metabolism and radiation response

监测癌细胞代谢与放射反应之间的相互作用

• 批准号: 10001058
• 负责人: Aparna Kesarwala
• 金额: $ 24.9万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001058
• 关键词: Antioxidants; Biophysics; Brain Neoplasms; Cancer Patient; Cellular biology; Characteristics; Citric Acid Cycle; Clinical; Clinical Trials; Combination Drug Therapy; Committee Members; Development Plans; Dose; Environment; Enzymes; Equilibrium; Foundations; Functional Magnetic Resonance Imaging; Future; Gluconeogenesis; Goals; Head; Heterogeneity; Hypoxia; Image; Individual; Investigation; Isocitrate Dehydrogenase; Knowledge; Learning; Magnetic Resonance Imaging; Mediating; Mentors; Metabolic; Metabolic Pathway; Metabolism; Molecular; Molecular Target; Monitor; Mutation; NADP; National Cancer Institute; Normal Cell; Pathway interactions; Pentosephosphate Pathway; Phase; Pyruvate; Pyruvate Metabolism Pathway; Radiation; Radiation Oncologist; Radiation Oncology; Radiation Tolerance; Radiation therapy; Radiobiology; Radiosensitization; Research; Research Personnel; Solid Neoplasm; Spectrum Analysis; Structure; Testing; Therapeutic; Therapy Clinical Trials; Time; Training; Training Programs; Tumor Biology; Warburg Effect; Work; aerobic glycolysis; alpha ketoglutarate; base; cancer cell; career; career development; clinical practice; clinically relevant; design; improved; in vivo; individual patient; innovation; interest; metabolic imaging; molecular imaging; mutant; novel; personalized medicine; programs; radiation effect; radiation response; real-time images; small molecule; spectroscopic imaging; targeted therapy trials; tumor; tumor metabolism

PROJECT SUMMARY/ABSTRACT Over half of cancer patients receive radiation therapy during their course of treatment, but the current clinical practice of radiation oncology does not adjust volumes or doses based on molecular characteristics of an individual patient’s tumor. The existing knowledge gap between tumor biology and clinical practice limits the ability to personalize radiation therapy. Dr. Kesarwala’s long-term scientific goal is to improve the efficacy of radiation therapy by personalizing concurrent therapies and radiation volumes and doses based on metabolic characteristics of tumors. She proposes to approach this goal via investigation and characterization of the interacting effects of radiation therapy, IDH1 mutations, and hypoxia on the metabolic pathways of cancer cells. This proposal is designed to test the hypothesis that altering cancer cell metabolism can increase radiation response. The goals of this proposal are to characterize the effects of 1) radiation therapy, 2) IDH1 mutations, and 3) hypoxia on metabolic balance, and 4) develop small molecules for metabolic imaging. The results from this research will significantly improve understanding of a potential target pathway for combination drug and radiation therapy and lay the foundation for future radiation therapy clinical trials. During the mentored phase of this proposal, she will expand upon her background in molecular imaging and cell biology and her clinical training in radiation oncology with additional study of cancer cell metabolism and metabolic imaging. She will be mentored by Dr. Kevin Camphausen, Senior Investigator and Chief of the Radiation Oncology Branch at the National Cancer Institute (NCI), a translational radiation oncologist who is an expert in brain tumors and clinical trials. Her co-mentor for this proposal is Dr. Murali Krishna Cherukuri, Senior Investigator and Head of the Biophysical Spectroscopy Section of the Radiation Biology Branch at the NCI, a leader and innovator in functional magnetic resonance imaging and spectroscopy. Her training program represents a thoughtful approach to the transition to independence, combining guidance from an outstanding team of mentors and mentoring committee members with formal coursework, a strong career development plan, and the exceptional training environment of the NCI. The work outlined in this proposal will be the next step towards Dr. Kesarwala’s long-term career goal, which is to become an independent investigator working at the interface of radiation oncology, cancer metabolism, and molecular imaging.

项目总结/摘要 超过一半的癌症患者在治疗过程中接受放射治疗，但目前的临床 放射肿瘤学的实践并不基于肿瘤的分子特征来调整体积或剂量。 个别患者的肿瘤。肿瘤生物学和临床实践之间存在的知识差距限制了肿瘤治疗的发展。 个性化放射治疗的能力。Kesarwala博士的长期科学目标是提高 通过基于代谢的个体化同步治疗和放射体积和剂量的放射治疗 肿瘤的特征。她建议通过调查和表征这一目标， 放射治疗、IDH 1突变和缺氧对癌症代谢途径的相互作用 细胞这项提议旨在验证一个假设，即改变癌细胞的新陈代谢可以增加 辐射反应该提案的目标是表征1）放射治疗，2）IDH 1 突变，和3）代谢平衡的缺氧，和4）开发用于代谢成像的小分子。的 这项研究的结果将大大提高对联合治疗的潜在靶向途径的理解。 药物和放射治疗，并为未来的放射治疗临床试验奠定基础。期间 在这个建议的指导阶段，她将扩展她在分子成像和细胞生物学方面的背景 以及她在放射肿瘤学方面的临床培训，以及对癌细胞代谢和代谢的额外研究， 显像她将由高级研究员兼辐射主任Kevin Camphausen博士指导 国家癌症研究所（NCI）肿瘤学分支，一位翻译放射肿瘤学家， 脑肿瘤和临床试验她的共同导师是Murali Krishna Cherukuri博士，高级 NCI放射生物学分支生物物理光谱学研究员兼负责人， 功能性磁共振成像和波谱学领域的领导者和创新者。她的训练计划 代表了一个深思熟虑的方法过渡到独立，结合指导，从一个杰出的 导师团队和指导委员会成员，具有正式的课程，强大的职业发展 计划，以及NCI的特殊培训环境。本建议中概述的工作将是下一个 朝着Kesarwala博士的长期职业目标迈出了一步，这是成为一名独立的研究人员， 在放射肿瘤学、癌症代谢和分子成像的界面上。