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

项目摘要 在对PQ11的回答中，饮食和营养干预通过什么机制影响对 癌症治疗？“这项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，减少毒性反应。乳腺癌是 女性脑转移的主要原因，并与预后不良有关，尽管标准 包括放射治疗或手术切除在内的治疗。脑转移瘤的局部控制可提供更好的生存和 防止神经功能衰退。为了尝试和改善局部控制，已经添加了新的靶向疗法 辐射(RT)；不幸的是，大多数在增加显著毒性的同时几乎没有改善。对于 第一次，将确定改变饮食是否会在脑转移瘤的治疗中发挥作用 由于转移和肿瘤细胞对RT耐药的特征之一是细胞调节失调 新陈代谢。我们的长期目标是1)通过赋予患者使用 饮食干预以改善结果，以及2)利用这项建议的发现来翻译 调查结果。这笔赠款的目的是确定是否可以提高对转移性疾病的放射疗效。 而不会增加毒性，通过饮食控制。中心假设是，一个完整的 一种结合饮食变化的方法，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，从而提高患者存活率。我们的具体目标将检验以下假设： (AIM1)确定饮食干预对乳房放射治疗效果的贡献 (目的2)IGF-1R/AKT信号通路轴是一个关键节点，至少在某些部分， 在生物反应导致建议的分子细胞毒性之间的协同饮食 改良和RT；(目的3)确定乳腺癌脑转移患者中受益的亚组 来自DM和RT的组合。这一贡献意义重大，因为它将确立饮食调整可以 靶途径(即IGF-1R/Akt)调节辐射反应并影响积极的临床变化。这个 拟议中的研究是创新的，因为饮食在癌症治疗中并未被用作“药物”。这 该提案将提供如何利用饮食调整来影响辐射反应的见解， 乳腺癌脑转移患者的潜在毒性和预后。

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.