Fatty Acid Synthase Phosphorylation as a Cancer Biomarker

脂肪酸合酶磷酸化作为癌症生物标志物

• 批准号: 7413700
• 负责人: Susan Medghalchi
• 金额: $ 10万
• 依托单位: FASGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7413700
• 关键词: Advanced Development; Aliquot; Amino Acids; Anions; Antibodies; Apoptosis; Binding; Biological Assay; Biological Markers; Blood; Blood Tests; Breast; Cancer Detection; Cancer Patient; Cancer cell line; Cell Line; Chromatography; Colon; Data; Development; Diagnostic; Diamond; Dietary Carbohydrates; Digestion; Early Diagnosis; Elevation; Enzyme-Linked Immunosorbent Assay; Enzymes; Epitopes; Fatty Acids; Fatty Liver; Fatty-acid synthase; Gel; Gel Chromatography; Genus Cola; Goals; HCT116 Cells; Human; Hybridomas; Immunoblotting; Immunoprecipitation; In Vitro; Investigation; Label; Lasers; Liver; Liver diseases; Lung; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Maps; Measurement; Metabolic; Methods; Molecular Probes; Normal tissue morphology; Obesity; Ovarian; Ovary; Pancreas; Patients; Phase; Phosphoamino Acids; Phosphopeptides; Phosphorylation; Phosphorylation Site; Phosphoserine; Phosphothreonine; Phosphotyrosine; Pro-Q aerosol foam; Proline; Prostate; Protein Phosphatase Inhibitor; Quality of life; Serum; Site; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Specificity; Staining method; Stains; Steatohepatitis; Testing; Threonine; Tumor Cell Line; Two-Dimensional Gel Electrophoresis; base; cancer cell; cell transformation; in vivo; interest; malignant breast neoplasm; nonalcoholic steatohepatitis; therapeutic target; tumor

DESCRIPTION (provided by applicant): During the last decade, increasing interest has developed in fatty acid synthase (FAS) as a potential diagnostic and therapeutic target for human cancer. These notions are based on two fundamental observations: [1] FAS is highly expressed in most common human cancers, and [2] pharmacological inhibition of FAS leads to apoptosis of human cancer cells in vitro and in vivo. FAS is the enzyme which catalyzes the de novo synthesis of fatty acids predominantly from dietary carbohydrates. In addition to its expression in human cancers, our collaborators have found that FAS circulates at high levels in the blood of colon, breast, lung, ovarian, and prostate cancer patients compared to normal subjects. Recent data have emerged which directly impact FAS as a biomarker for cancer: [1] FAS elevations have been found to occur in the blood of obese subjects with non-alcoholic steatohepatitis, and [2] FAS derived from tumor cell lines is phosphorylated on threonine residues while FAS from non-transformed cells is not phosphorylated. These findings will enable the development of a diagnostic ELISA serum test for human cancer based on phosphorylated FAS which would not react with FAS derived from normal tissues such as liver. The goals of this Phase I SBIR are to determine that FAS derived from human cancer is selectively phosphorylated and detectable in the serum of cancer patients but not in the sera of obese subjects. This tumor selective phospho-FAS would form the basis for the development of a cancer-selective FAS ELISA assay for the Phase II application. The early diagnosis of cancer enables more effective therapy and enhances patient survival and quality of life. Fatty acid synthase is present at high levels in most common human cancers including colon, lung, prostate and breast cancer. The goal of this proposal is to advance the development of a blood test for cancer based on the identification of FAS which will broadly identify the presence of most human cancer.

描述（由申请人提供）：在过去的十年中，对脂肪酸合酶（FAS）的兴趣越来越多，作为人类癌症的潜在诊断和治疗靶标。这些概念基于两个基本观察：[1] Fas在大多数常见的人类癌症中高度表达，[2]药理学抑制FA会导致体外和体内人类癌细胞的凋亡。 FAS是一种酶，可催化从饮食中碳水化合物中主要从头合成脂肪酸。除了在人类癌症中的表达外，我们的合作者还发现，与正常受试者相比，FAS在结肠，乳腺癌，肺，卵巢和前列腺癌患者的血液中循环高水平。最近出现了直接影响FA的癌症生物标志物的数据：[1]发现FAS升高发生在非酒精性脂肪性肝炎的肥胖受试者的血液中，而[2] FAS源自肿瘤细胞系的FAS [2] FAS磷酸化，而在未转换细胞的FAS上磷酸化，而未转换细胞的FAS并未被磷酸化。这些发现将使基于磷酸化的FAS的诊断性ELISA血清测试为人类癌症的开发，该磷酸化FA不会与源自正常组织（如肝脏）的FA反应。 I阶段SBIR的目标是确定在癌症患者的血清中被选择性地磷酸化和可检测到的FA，但在肥胖受试者的血清中不可检测。该肿瘤选择性磷酸-FA将构成为II期应用开发癌症选择性FAS ELISA测定法的基础。癌症的早期诊断可以更有效的治疗，并增强患者的生存和生活质量。在大多数常见的人类癌症（包括结肠，肺，前列腺癌和乳腺癌）中，脂肪酸合酶存在于高水平。该提案的目的是基于FAS的鉴定来推进癌症血液测试的发展，而FA将广泛地识别大多数人类癌症的存在。