(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

• 批准号: 10439798
• 负责人: Nicole L Simone
• 金额: $ 34.97万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10439798
• 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; 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

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.

项目摘要 响应PQ11，“饮食和营养干预措施通过哪些机制影响对 癌症治疗吗？ 改善预后和降低脑转移乳腺癌患者的毒性。乳腺癌是 女性脑转移的主要原因，与惨淡的预后目的地标准有关 包括辐射或手术切除在内的疗法。局部控制脑转移可以承认更好的生存和 防止神经系统下降。为了尝试改善本地控制，已添加了新颖的靶向疗法 辐射（RT）;不幸的是，大多数人在增加毒性的同时几乎没有改善。为了 第一次，将确定饮食修饰是否可能在脑转移的治疗中起作用 由于转移酶和肿瘤细胞抗RT的标志之一是细胞失调 代谢。我们的长期目标是1）通过赋予患者的能力来改变癌症护理的景观 饮食干预措施以改善结果，2）使用此提案中的发现来翻译 发现。该赠款的目的是确定转移性疾病是否可以提高辐射效率 不使用饮食操纵而不会增加毒性。中心假设是综合 方法是一种纳入饮食变化，将改变转移性肿瘤细胞中关键的前寿途径， 改善局部控制，从而改善患者的生存。我们的具体目标将检验以下假设： （AIM1）确定饮食干预对乳房治疗的辐射效率的贡献 癌症脑转移； （AIM 2）IGF-1R/AKT信号通路轴是一个关键节点，至少在某些部分， 在生物学反应中，导致提出的分子细胞毒性合作 修改和RT； （AIM 3）确定有益于脑转移的乳腺癌患者的子集 从组合的DMS和RT。这项贡献很重要，因为它将确定饮食修改可以 目标途径（IE IGF-1R/AKT）调节辐射反应并影响正临床变化。 拟议的研究具有创新性，因为饮食在癌症治疗过程中尚未用作“药物”。这 提案将提供有关如何使用饮食修饰来影响辐射反应的洞察力， 脑转移乳腺癌患者的潜在毒性和结果。

项目成果

An Ex Vivo Brain Slice Model to Study and Target Breast Cancer Brain Metastatic Tumor Growth.

• DOI: 10.3791/62617
• 发表时间: 2021-09-22
• 期刊: Journal of visualized experiments : JoVE
• 作者: Ciraku L;Moeller RA;Esquea EM;Gocal WA;Hartsough EJ;Simone NL;Jackson JG;Reginato MJ
• 通讯作者: Reginato MJ

The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View

• DOI: 10.1016/j.trecan.2020.01.004
• 发表时间: 2020-03-01
• 期刊: TRENDS IN CANCER
• 影响因子: 18.4
• 作者: Xavier, Joao B.;Young, Vincent B.;Wargo, Jennifer A.
• 通讯作者: Wargo, Jennifer A.