Monitoring the interactions between cancer cell metabolism and radiation response

项目摘要/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 放射肿瘤学的实践不会根据肿瘤的分子特征调整体积或剂量 个别病人的肿瘤。肿瘤生物学和临床实践之间存在的知识差距限制了 个性化放射治疗的能力。Kesarwala博士的长期科学目标是提高 基于代谢的个性化同步治疗和辐射体积和剂量的放射治疗 肿瘤的特征。她建议通过调查和描述 放射治疗、IDH1突变和低氧对肿瘤代谢途径的交互作用 细胞。这项提议旨在验证改变癌细胞新陈代谢可以增加 辐射反应。这项建议的目标是描述1)放射治疗的效果，2)IDH1 突变，以及3)代谢平衡的低氧，以及4)开发用于代谢成像的小分子。这个 这项研究的结果将显著提高对潜在靶向结合途径的理解 药物和放射治疗，并为未来放射治疗的临床试验奠定基础。在.期间 在这项提议的指导阶段，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 成像。她将得到高级研究员兼放射科主任凯文·卡普森博士的指导 美国国家癌症研究所(NCI)肿瘤学分部，一位翻译放射肿瘤学家，他是 脑瘤和临床试验。她这项提议的共同导师是Murali Krishna Cherukuri博士，资深 美国国立卫生研究院辐射生物学分会生物物理光谱科科长、研究员 功能磁共振成像和光谱学领域的领导者和创新者。她的培训计划 代表了向独立过渡的深思熟虑的方法，结合了来自杰出的 团队的导师和辅导委员会成员具有正规的课程工作，有很强的职业发展能力 计划，以及NCI特殊的培训环境。这项提案中概述的工作将是下一步 迈向凯萨尔瓦拉博士的长期职业目标，那就是成为一名独立的调查员 在放射肿瘤学、癌症新陈代谢和分子成像的界面上。

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.