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

项目摘要 针对方案问题11，“饮食和营养干预通过何种机制影响对 癌症治疗？”该提案将确定营养可用于改善辐射（RT）反应， 改善脑转移乳腺癌患者预后并降低毒性。乳腺癌是 是女性脑转移的主要原因，尽管标准的 治疗包括放射或手术切除。局部控制脑转移瘤可提高生存率， 防止神经功能衰退为了尝试和改善局部控制，新的靶向治疗已被添加到 辐射（RT）;不幸的是，大多数都没有带来什么改善，同时增加了显着的毒性。为 这将是第一次确定饮食调整是否可以在治疗脑转移瘤中发挥作用。 由于转移和肿瘤细胞对RT的抗性的标志之一是细胞凋亡的失调， 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，和2）使用这项建议的发现， 调查结果。该补助金的目的是确定是否可以增加转移性疾病的放射疗效 而不增加毒性。核心假设是， 一种结合饮食改变的方法，将改变转移性肿瘤细胞中关键的促生存途径， 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： （目标1）确定饮食干预对乳腺癌治疗中放射有效性的贡献 癌症脑转移;（目的2）IGF-1 R/AKT信号传导途径轴是关键节点，至少在某些部分， 在生物反应中，导致饮食之间的分子细胞毒性合作， （目的3）确定脑转移的乳腺癌患者的亚组， 这一贡献是重要的，因为它将确定饮食调整可以 靶向途径（即IGF-1 R/Akt）调节辐射反应并影响积极的临床变化。的 建议的研究是创新的，因为饮食在癌症治疗中没有被用作“药物”。这 该提案将深入了解如何通过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局。

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.