Identifying factors regulating cancer metabolism in vivo

项目摘要 代谢改变是恶性肿瘤的标志。代谢途径的变化有助于癌细胞的生长， 转型与生存这些差异可以用于对肿瘤组织进行成像，并提供预测性信息。 给病人的信息。重要的是，这些代谢差异也可以用于治疗。因此，在本发明中， 了解癌症代谢对病理生理学和临床肿瘤学具有重要意义。 将这些研究转化为新疗法的进展受到以下事实的限制： 代谢是从培养细胞的研究中获得的，与疾病生物学的相关性未知。同样，Cell 线异种移植物可能不能准确地概括原发性肿瘤的细胞异质性。由于这些原因， 对体内肿瘤代谢以及调节这种行为的因素知之甚少。我的提议利用了 临床样品，其中评价和表征所述原发性人肿瘤的代谢行为。 将这些组织转化为小鼠模型，在那里我将评估保留了哪些代谢表型， 以及测试哪些内在和外在因素促进代谢行为。在辅导阶段， 格兰特，我将专注于确定保留/内在代谢表型，以及外在因素，如 肿瘤灌注对营养偏好的作用。有了这些见解，我将继续独立研究重点， 这些因素的分子细节，以确定影响癌症代谢的因素组合， vivo.

Project Summary Altered metabolism is a hallmark of malignancy. Metabolic pathway changes contribute to cancer cell growth, transformation and survival. These differences can be exploited to image tumor tissue and provide predictive information to patients. Importantly, these metabolic differences can also be exploited therapeutically. Thus, understanding cancer metabolism has important implications for pathophysiology and clinical oncology. Progress in translating these studies into new therapies is limited by the fact that much of knowledge in tumor metabolism is derived from studies in cultured cells with unknown relevance to disease biology. Similarly, cell line xenografts may not accurately recapitulate the cellular heterogeneity of a primary tumor. For these reasons, little is known about tumor metabolism in vivo, and the factors that regulate this behavior. My proposal utilizes clinical samples wherein the metabolic behavior of the primary human tumor is evaluated and characterized. These tissues are translated to mouse models, where I will evaluate what metabolic phenotypes are retained, as well as test what intrinsic and extrinsic factors promote metabolic behavior. During the mentored phase of the grant, I will focus on identifying retained/intrinsic metabolic phenotypes, as well as extrinsic factors such as the role of tumor perfusion on nutrient preference. With these insights, I will continue independent research focusing on the molecular details of these factors, to identify combinations of factors influencing cancer metabolism in vivo.