Targeting Lung Cancer Vulnerabilities

针对肺癌的脆弱性

• 批准号: 10816969
• 负责人: John V. Heymach
• 金额: $ 4.56万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10816969
• 关键词: Affect; Award; Cancer Etiology; Cessation of life; Clinical; Clinical Markers; Clinical Protocols; Consumption; Data; Disease Progression; Excision; Funding; Genetically Engineered Mouse; Glucose; Goals; Heterogeneity; Human; Intravenous infusion procedures; Label; Lung; Lung Neoplasms; Malignant neoplasm of lung; Mass Spectrum Analysis; Metabolic; Metabolism; Mus; Neoplasm Metastasis; Non-Malignant; Non-Small-Cell Lung Carcinoma; Operative Surgical Procedures; Outcome; Parents; Patients; Pre-Clinical Model; Property; Pulmonary Coin Lesion; Signal Transduction; Source; Surgeon; Survival Rate; Techniques; Testing; Texas; Therapeutic; Therapeutic Effect; Tissue Extracts; Tissue Sample; Tracer; Translating; Universities; Xenograft procedure; anti-tumor immune response; fluorodeoxyglucose positron emission tomography; improved; in vivo; innovation; metabolic phenotype; mouse model; neoplastic cell; new therapeutic target; parent project; predictive marker; recruit; stable isotope; therapeutic biomarker; tumor; tumor growth; tumor metabolism; tumor microenvironment

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.

摘要 受资助家长奖及项目摘要。父项目的总体目标，5P50CA070907-23 (德克萨斯大学的肺癌孢子，《瞄准肺癌的脆弱性》)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：“瞄准新陈代谢弱点 在肺癌方面。“该项目的中心假设是人类非小细胞的代谢表型 肺癌(NSCLC)可以提供新的治疗靶点和生物标记物来预测 治疗敏感性和临床结果。该项目使用最先进的方法来评估 用稳定同位素示踪剂研究人肺肿瘤的代谢。在这种方法中，孤立性肺病患者 将结节纳入临床方案(NCT01668082)，并在治疗期间静脉输注13C-葡萄糖 手术切除肿瘤和邻近的肺。从组织样本中提取的代谢物 然后通过质谱学对外科医生进行评估，以比较肿瘤和邻近组织之间的13C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， 识别体内人类肿瘤消耗的代谢燃料，并将肿瘤的代谢特性与 临床指标包括FDG-PET信号及结果1-3。