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; 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.

概括 资助父母奖和项目的摘要。父母项目的总体目标，5P50CA070907-23 （德克萨斯大学肺癌孢子，“针对肺癌脆弱性”）是确定责任 在人类肺癌中，了解这些脆弱性的机械基础并发展治疗 可以在患者中部署的策略。 Deberardinis博士领导项目1：“针对代谢漏洞 在肺癌中。 肺癌（NSCLC）可以提供预测的新治疗靶标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 使用稳定的同位素示踪剂对人肺肿瘤的代谢。在这种方法中，固体肺的患者 结节招募到临床方案（NCT01668082），并在静脉内注入13c-葡萄糖。 肿瘤和邻近肺的手术切除。从组织样品中提取的代谢产物 然后，通过质谱法评估外科医生，以比较肿瘤和相邻之间的13C标记， 非恶性肺。我们已经使用这种方法来评估肿瘤中代谢异质性的原因， 鉴定体内人类肿瘤消耗的代谢燃料，并将肿瘤的代谢特性与 包括FDG-PET信号和结果1-3在内的临床标记。