2015-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/658235摘要：肺癌在全世界是一個造成疾病死亡率相當高的疾病，近年來由於化學治療與標靶治療的進步使得肺癌患者的存活延長。雖然如此，化學治療與標靶藥物的使用仍然會有抗藥性的出現。如何預測化學治療與標靶藥物的療效，與避免抗藥性將有助於改善肺癌患者的存活。然而，不同的 EGFR 突變測試有不同的靈敏度同時肺癌組織也不容易取得因此限制了臨床上的使用。由於肺癌是惡性肋膜積液最常見的原因，而且肺癌患者時常需要抽取肋膜積液以緩解症狀。因此，肋膜積液是一個生物標記檢測理想的 biofluid，可作為預測化學治療與標靶治療（如 EGFR 或 EML4 - ALK 抑製劑）在肺癌患者的治療效果與性耐藥的產生。代謝體學（metabolomics）為系統生物學(systems biology)中質體學（”omics”）的一部份，其主要為整體而大規模的量測不同生理狀態下的體內代謝物(metabolites)分布。由於基因表現於生物體最終是以代謝物的方式呈現，因此一些環境或疾病的變化最終都會造成代謝物濃度與分布的改變。比較不同疾病或狀態下代謝物分布的改變，可以了解基因表現及各種蛋白質作用所帶來的變化，因而代謝體的研究方法可視為整合性的評估多項生物體途徑與反應最終結果。許多研究利用 NMR 或 MS，來探討其在疾病的早期診斷、預後判斷、與監測治療反應上的應用與角色。在本研究中，我們希望應用代謝體學來探討不同成因的肋膜液中代謝物與代謝體的變化，希望能藉此發現與肋膜液成因相關的生物標記，與預測肺癌標靶治療的效果。希望進一步闡釋關連的生物機轉與作用路徑。<br> Abstract: Lung cancer is the leading cause of cancer deaths worldwide, chemotherapy with platinum doublet is the main first-line treatment modality for advanced non-small-cell lung cancer (NSCLC). About 30% of advanced NSCLC patients treated with platinum doublets chemotherapy achieve a response that lasts 4–5 months. However, about 40-50% of these patients experienced progressive disease with frontline platinum doublet chemotherapy. There was no clinical relevant predictive factor for choosing chemotherapeutic agent to improving treatment outcome. Hence, the use of molecular predictive markers to help identifying who may benefit and who may not remains one of the most exciting new areas of study in oncology. In addition to chemotherapy, efforts to improve the survival of these patients is currently focused on new target-based therapies directed against key signaling pathways involved in lung cancer growth and malignant progression. Among these, patient EGFR mutational status is the best predictor of benefit from EGFR TKI therapy. However, variable sensitivity of EGFR mutation tests and lung cancer tissue unavailability lead to limited clinical use. Lung cancer is the most common cause of malignant pleural effusion, and we perform thoracentesis frequently on an out patient basis for diagnosis testing and symptomatic relief. Therefore, pleural effusion is an ideal biofluid for markers detection, which may predict treatment response and acquired resistance of target-based therapies (such as EGFR or EML4-ALK inhibitors) in lung cancer patients. Metabolomics, an omic science in systemic biology, is the global quantitative assessment of endogenous metabolites within a biological system. Advances in metabolic profiling technologies and methods of pattern recognition enable the monitoring of hundreds of metabolites from tissue or body fluids associated with disease physiology. Metabolomics, when used as a translational researchtool, can provide a link between the laboratory and clinic. The current proposal is aimed to establish the metabolomic profiling of pleural effusions to predict treatment response and acquired resistance of target-based therapies in lung cancer patients代謝體學肋膜液肺癌肺癌化學治療標靶治療metabolomicspleural effusion lung cancerchemotherapytarget-based therapy