(11) Diet Modification to Augment Radiation for Breast Cancer Brain Metastases

(11) 调整饮食以增强乳腺癌脑转移的放射治疗

基本信息

批准号：
10206051
负责人：
Nicole L Simone
金额：
$ 35.69万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10206051
关键词：
AKT Signaling Pathway Address Adverse event Affect Applications Grants Biological Body mass index Brain Breast Cancer Model Breast Cancer Patient Breast Cancer Treatment Caloric Restriction Cancer Prognosis Caring Clinical Clinical Trials Clinical Trials Design Data Diet Diet Modification Dietary Intervention Disease Effectiveness Energy Intake Estrogens Excision Fasting Fatigue Goals Grant Headache Health Hypoxia Impaired cognition Insulin-Like Growth Factor I Laboratories Lead Lesion Link Malignant Neoplasms Measures Memory Memory Loss Metabolic Metabolism Metastatic Neoplasm to the Lung Metastatic malignant neoplasm to brain Metastatic to Methods Micrometastasis Modality Molecular Nausea and Vomiting Neoplasm Metastasis Neurocognitive Neurologic Notch Signaling Pathway Operative Surgical Procedures Outcome Pathway interactions Patient-Focused Outcomes Patients Pharmaceutical Preparations Play Primary Neoplasm Prognosis Progression-Free Survivals Proteins Public Health Quality of life Radiation Radiation Toxicity Recurrence Reporting Research Resistance Role Serum Markers Short-Term Memory Signal Pathway Symptoms Testing Time Toxic effect Translating Trastuzumab Treatment Efficacy Weight Woman acute toxicity age related brain tissue breast cancer survival cancer care cancer therapy cytotoxic dietary dietary manipulation disorder control effective therapy empowered first-in-human improved improved outcome in vivo inhibitor/antagonist innovation insight insulin secretion ketogenic diet knock-down malignant breast neoplasm member mind control neoplastic cell new therapeutic target novel novel therapeutics nutrition obese patients overexpression patient subsets pre-clinical prevent radiation response response targeted treatment therapy resistant tumor tumor metabolism tumor microenvironment tumor progression

项目摘要

Project Summary In response to PQ11, “Through what mechanisms do diet and nutritional interventions affect the response to cancer treatment?,” this proposal will determine that nutrition can be used to improve radiation (RT) response, improve outcomes and decrease toxicity for breast cancer patients with brain metastases. Breast cancer is the leading cause of brain metastases in women and is associated with a dismal prognosis despite standard therapies including radiation or surgical resection. Local control of brain metastases confers better survival and prevents neurological decline. To try and improve local control, novel targeted therapies have been added to radiation (RT); most have unfortunately resulted in little improvement while adding significant toxicity. For the first time, it will be determined if dietary modifications may play a role in the treatment of brain metastases since one of the hallmarks of both metastases and tumor cell resistance to RT, is the dysregulation of cellular metabolism. Our long-term goal is to 1) change the landscape of cancer care by empowering patients to use dietary interventions to improve outcomes, and 2) to use the discoveries from this proposal to translate findings. The objective of this grant is to determine if radiation efficacy can be increased for metastatic disease without increasing toxicity, by using dietary manipulation. The central hypothesis is that an integrated approach, one incorporating dietary changes, will alter key pro-survival pathways in metastatic tumor cells, to improve local control and, therefore, patient survival. Our specific aims will test the following hypotheses: (Aim1) Determine the contribution of dietary intervention on radiation effectiveness in treatment of breast cancer brain metastases; (Aim 2) the IGF-1R/AKT signaling pathway axis is a key node, at least in some part, in the biological response leading to the proposed molecular cytotoxic cooperation between dietary modification and RT; (Aim 3) Determine the subset of breast cancer patients with brain metastases that benefit from combined DMs and RT. This contribution is significant since it will establish that dietary modifications can target pathways (ie IGF-1R/Akt) to modulate the radiation response and affect a positive clinical change. The proposed research is innovative because diet has not been used as a “drug” during cancer therapy. This proposal will provide insight into how dietary modifications can be used to affect the radiation response, potential toxicity and outcomes in breast cancer patients with brain metastases.

项目概要针对 PQ11，“饮食和营养干预通过什么机制影响对癌症治疗？”该提案将确定营养可用于改善放射（RT）反应，改善乳腺癌脑转移患者的预后并降低毒性。女性脑转移的主要原因，尽管有标准，但仍与不良预后相关包括放射或手术切除在内的治疗可提高生存率和脑转移的局部控制。为了尝试改善局部控制，添加了新的靶向疗法。不幸的是，辐射（RT）几乎没有改善，同时增加了显着的毒性。首次将确定饮食改变是否可以在脑转移瘤的治疗中发挥作用由于转移和肿瘤细胞对放疗的抵抗的标志之一是细胞的失调我们的长期目标是 1) 通过赋予患者使用代谢的能力来改变癌症护理的格局。饮食干预以改善结果，以及 2) 利用本提案的发现来转化此项资助的目的是确定是否可以提高转移性疾病的放射疗效。在不增加毒性的情况下，通过饮食控制来实现这一目标的核心假设是综合的。一种结合饮食改变的方法将改变转移性肿瘤细胞的关键促生存途径，以改善局部控制，从而提高患者的生存率，我们的具体目标将检验以下假设：（目标1）确定饮食干预对乳腺放射治疗效果的贡献癌症脑转移；（目标 2）IGF-1R/AKT 信号通路轴是关键节点，至少在某些部分，在生物反应中导致拟议的饮食之间的分子细胞毒性合作修改和 RT；（目标 3）确定可受益的脑转移乳腺癌患者亚群来自 DM 和 RT 的结合这一贡献非常重要，因为它将确定饮食调整可以靶途径（即IGF-1R/Akt）来调节放射反应并影响积极的临床变化。拟议的研究具有创新性，因为饮食在癌症治疗过程中并未被用作“药物”。该提案将深入了解如何利用饮食调整来影响辐射反应，乳腺癌脑转移患者的潜在毒性和结果。