Targeting Lung Cancer Vulnerabilities

总结 资助的家长奖和项目摘要。母项目总体目标，5 P50 CA 070907 -23 (The得克萨斯大学肺癌研究中心的“靶向肺癌脆弱性”）是为了确定责任 在人类肺癌中，了解这些脆弱性的机制基础，并开发治疗方法。 可以在患者身上部署的策略。DeBerardinis博士领导项目1：“针对代谢脆弱性” 肺癌的症状该项目的中心假设是，人类非小细胞代谢表型 肺癌（NSCLC）可以提供新的治疗靶点和生物标志物的来源， 治疗敏感性和临床结果。该项目采用最先进的方法来评估 使用稳定同位素示踪剂的人肺肿瘤代谢。在这种方法中， 将结节招募到临床方案（NCT 01668082）中，并在治疗期间静脉输注13 C-葡萄糖。 手术切除肿瘤和邻近肺。从组织样本中提取的金属 然后通过质谱法评估外科医生以比较肿瘤和邻近肿瘤之间13 C标记， 非恶性肺。我们已经使用这种方法来评估肿瘤之间代谢异质性的原因， 确定人体肿瘤在体内消耗的代谢燃料，并将肿瘤的代谢特性与 临床标志物，包括FDG-PET信号和结局1 -3。

SUMMARY Summary of Funded Parent Award and Project. The overall goal of the parent project, 5P50CA070907-23 (The University of Texas SPORE in Lung Cancer, “Targeting Lung Cancer Vulnerabilities”) is to identify liabilities in human lung cancer, understand the mechanistic basis of these vulnerabilities and develop therapeutic strategies that can be deployed in patients. Dr. DeBerardinis leads Project 1: “Targeting Metabolic Vulnerabilities in Lung Cancer.” The central hypothesis of this Project is that metabolic phenotypes in human non-small cell lung cancer (NSCLC) can provide a source of new therapeutic targets and biomarkers that predict therapeutic sensitivities and clinical outcomes. The Project uses a state-of-the-art approach to assess metabolism of human lung tumors using stable isotope tracers. In this approach, patients with solitary pulmonary nodules are recruited to a clinical protocol (NCT01668082) and intravenously infused with 13C-glucose during surgical resection of the tumor and adjacent lung. Metabolites extracted from tissue samples procured by the surgeon are then assessed by mass spectrometry to compare 13C labeling between tumor and adjacent, nonmalignant lung. We have used this approach to assess the causes of metabolic heterogeneity among tumors, identify metabolic fuels consumed by human tumors in vivo and correlate the metabolic properties of tumors with clinical markers including FDG-PET signal and outcomes1-3.