Tumor Evolution and Changes in Metabolism

研究项目2（RP 2）是基于ICMIC 2期间的初步数据和研究。目标 该项目的目的是开发非侵入性方法来区分惰性和侵袭性癌症， 监测肿瘤向更恶性状态的演变。这些非常务实的癌症护理问题是 与许多患者相关，具有很高的潜在影响。该项目的中心主题是 将非侵入性成像技术整合到新模式的开发中，以推进癌症护理。在Aim中 1.我们建议确定乳酸盐升高是否是遗传性肿瘤的一般特征， 我们的目标是更广泛的，是确定这是否是一个普遍的， 具有更具侵袭性/转移性肿瘤表型的特征。由于PTEN/PI 3 K/AKT突变和 缺失通常存在于侵袭性/转移性肿瘤中，并且是预后不良的因素。 多种肿瘤类型，我们专注于这个信号通路。一系列跨广泛的同基因肿瘤 将研究一系列癌症（乳腺癌、前列腺癌、结肠癌、神经胶质瘤）。我们将确定乳酸水平，LDHA 表达、葡萄糖和谷氨酰胺代谢以及基因阵列谱是一致的。我们将 确定MRS确定的代谢变化/差异是否与^^FDG的测量结果一致 摄取，基因阵列概况分析（与RP 4合作），和表型行为（生长， 转移）。在目标2中，我们将确定LDH-A是否是潜在的 开发新的抗肿瘤药物的重要靶点，以及MRS测量是否可用作 一种非侵入性的目标抑制方法。在目标3中，我们将与RP 3和RP 4合作，以确定 代谢的变化可用作对新的特异性靶向治疗的反应的早期标记。 我们将对正在或即将进入临床的新疗法进行MRS和PET（RP 4）研究。 评价我们假设，成功的治疗将诱导较低的糖酵解（和氨解）状态 并且将反映在肿瘤代谢（乳酸水平、糖酵解和精氨酸分解率以及FDG）中。 摄取）。我们的长期目标是将本项目中获得的临床前MR成像结果转化为 比较临床影像学研究。

Research Project 2 (RP2) is based on preliminary data and studies performed during ICMIC 2. The goal of this project is to develop non-invasive methods to distinguish indolent from aggressive cancers and to monitor evolution of a tumor to a more malignant state. These very pragmatic issues of cancer care are relevant to many patients and are of high potential impact. The central theme of this project is the integration of non-invasive imaging in the development of new paradigms to advance cancer care. In Aim 1 we propose to determine whether elevated lactate is a general characteristic of tumors with genetic mutations activating the PTEN/PI3K/AKT, Our goal is broader and is to determine whether this is a general characteristic of a more aggressive/metastatic tumor phenotype. Since PTEN/PI3K/AKT mutations and deletions are commonly present in aggressive/metastatic tumors and a poor prognostic factor across multiple tumor types, we focus on this signaling pathway. A series of isogenic tumors across a broad range of cancers (breast, prostate, colon, glioma) will be studied. We will determine if lactate levels, LDHA expression, glucose and glutamine metabolism, and gene array profiles are concordant. We will determine if the MRS-determined metabolic changes/differences are concordant with measures of ^^FDG uptake, gene array profile analyses (in collaboration with RP4), and phenotypic behavior (growth, metastases) in prostate and other tumor models. In Aim 2 we will determine if LDH-A is potentially an important target for developing new anti-neoplastic drugs and whether MRS measurements can be used as a non-invasive measure of target inhibition. In Aim 3 we will collaborate with RP 3 and 4 to determine if changes in metabolism can be used as an early marker of response to novel specific targeted therapies. We will perform MRS and PET (RP4) studies on novel therapies that are, or will shortly be in clinical evaluation. We hypothesize that successful therapy will induce a lower glycolytic (and glutaminolytic) state and will be reflected in tumor metabolism (lactate levels, glycolytic and glutaminolytic rates and ^^FDG uptake). Our long term goal is to translate the preclinical MR imaging results obtained in.this project to comparable clinical imaging studies.