摘要:本院延續第一期計畫,由「癌症卓越研究中心」,整合本院現有各癌症臨床服務團隊與醫學院各大核心實驗室與中心,以發揮本院團隊綜效。此次以四個癌症研究團隊及癌症生物標記整合及服務中心CBCSC為架構,從事跨領域、整合性的癌症創新與轉譯研究,將成果匯集轉譯為癌症之新治療藥物或技術;發展出癌症早期預防、診斷與治療之方法,提昇癌症的診療成效,以期降低國人的癌症的死亡率。(乳癌團隊) 針對發生率上升及早發性特色的臺灣女性乳癌,發展具有成本效益的篩檢方法和避免過度治療的策略: (1)將鑑定出的致病相關環境賀爾蒙、基因多樣性及家族史結合成一個危險度預測模式,以早期篩檢或預防措施。(2)採用本校研發的超音波影像定位及記錄系統,並建立乳房超音波的標準篩檢程序,並在多個醫學中心試驗及將收集的影像做電腦輔助偵測和診斷之研究。(3)藉由臨床病理特徵,基因多形性和分子圖譜之整合分析,發展乳腺管原位癌個人化醫療,以減少健保支出及免除放射治療的長期副作用。(4)利用蛋白質體分析技術,找出早期檢測乳癌的血漿蛋白生物標記,以應用於早期乳篩和監控醫療效果。(5)考量實用及成本,發展IHC4 plus平台( ER、PR、HER2及Ki67,並加上單一基因或分子TP53突變及FOXA1、 LKB1、 p4EBP),以期急遽增加luminal型年輕乳癌避免過度使用化學治療。(大腸直腸癌團隊),(1)早期大腸直腸癌篩檢工具與策略之創新研究:(免疫法糞便潛血檢查對於大型腺瘤與大腸直腸癌敏感度研究、以病理特徵與分子特徵研究T1大腸癌合併淋巴轉移的危險因子、不同外型大腸直腸腫瘤的分子特徵與生物標記之發展)。(2) 以代謝體分析(2000年、2010年收集的大腸直腸癌組織代謝物間的差異)找尋大腸直腸癌的發生影響因子。(3) 建立大腸直腸癌生物標誌導向之個人化醫療:以新型專利方法偵測循環腫瘤細胞用於早期偵測大腸直腸癌復發、著重於KRAS基因突變大腸直腸癌探討其較有效化學治療背後隱藏之機轉、以腹腔鏡以及機械手臂手術進行根治性淋巴腺廓清術,來增加後期大腸直腸癌病患的五年存活率至40%,並藉此來發現預後因子以及新型生物標誌。(4) 應用創新奈米藥物傳輸技術於大腸直腸癌造影與毒殺。(血癌團隊) 前期計畫已發現一些基因突變與病人的臨床表現及預後息息相關,以此為基礎擴大研究,以期達到個人化醫療的理念。(1)根據最新WHO所訂定的分類來診斷病人,把染色體變化與基因突變融入分類的標準,以便更精準預測病人預後;與其他醫學中心的合作,建立台灣完整、正確的急性骨髓性白血病資料庫,做為流行病學及公共衛生政策擬定的基石;(2)除了WHO最新AML分類(NPM1與CEBPA突變)外,加入新的基因突變(RUNX1, FLT3/ITD與KIT突變)、基因及miRNA表現的檢測,以建立整合性疾病預後預測系統。(3)運用即時定量聚合酶鏈鎖反應與多色流式細胞儀來嚴密監控治療後的微量殘存疾病,以預測病人存活期甚至藉以改變治療策略以更符合每位病人的需求。(胰臟癌團隊) 本計畫的研究重點在早期篩檢、更佳的術前診斷分期工具、局部晚期的更佳較少侵入性治療、正確預測及篩選適當病患接受個人化治療的理想標記。(1)發展非傳統FDG的新式正子放射製劑,以及用利用傳統正子掃描,加強術前診斷遠端轉移的能力與評估其對手術可行性之臨床價值。(2)發展亞太地區第一個非可逆性電穿孔治療中心,使用於局部晚期胰臟癌治療,評估其臨床安全性與增加手術切除率的臨床價值。(3)針對台灣的偶發性及遺傳性胰臟癌之基因型與表現型做分析,並且比較各種早期篩檢工具的優缺點及成本效益,其中包含CA19-9、循環中的腫瘤細胞、磁振造影與內視鏡超音波等等方式的應用。(4)檢測病患之腫瘤組織與血液中的生物標記,用以預測病患預後。最終,利用這些生物標記建立預測模型,與現有治療指引做整合,以改善病患存活。(癌症生物標記整合及服務中心CBCSC),建置完整之生物標記檢測系統,提供社區服務,促成個人化治療之實現。整合台大醫院及台大醫學院現有的癌症相關部科、醫療核心設施與臨床檢驗部門。以四大團隊為架構開發新的重要癌症生物標記,並持續研究及推廣多項重要癌症生物標記。架設網頁以推廣癌症生物標記(cancer biomarkers),聘請專人負責聯繫以接受院外檢體。辦理癌症生物標記檢測之實驗室認證及單項目之PT認證(proficiency test)。辦理研討會、訓練課程,以培育人才。關鍵詞:乳癌、大腸直腸癌、血癌、胰臟癌、癌症生物標記
Abstract: In the next second period project (2014-2017), we set our goals to enhance the level of cancer research, to solve the mystery of special endemic cancers in Taiwan (e.g. young female breast cancer ), to develope new and effective methods of diagnosis and treatment (e.g. colorectal cancer & pancreatic cancer) , and to realize the personalized therapy (e.g. leukemia). Breast Cancer Team: Developing cost-effective strategies for breast cancer screening and Avoiding over-treatment in Taiwan, an area of increasing incidence and early onset. 1.A susceptibility prediction model based on environmental exposure and genetic factors for emerging early-onset female breast cancer in Taiwan. 2.Breast ultrasound screening standardization and quality control. 3.To develop personalized treatment for Taiwanese patients with ductal carcinoma in situ of breast through the combined analyses of clinicopathologic features, genetic polymorphism, and molecular profiles. 4.Screening and identification of plasma protein biomarkers for breast cancer via a new proteomic approach. 5.Optimizing hormonal therapy for emerging young women with luminal breast cancer in Taiwan: to avoid overtreatment by chemotherapy for young patients Colorectal Cancer Team: We fucus on optimizing early colorectal cancer screening strategy, and different novel aspect, like metabolomic analysis, personalzed therapy & nanomedicine. 1. Screening tools and innovative research strategies for early colorectal cancer. 2.Analysis of the factors affecting the incidence of colorectal cancer in Taiwan by metabolomic approach.3.Biomarker-driven personalized medicine in colorectal cancer treatment. 4.A pre-clinical, translational study of multifunctional active targeting nanomedicine in the management of advanced colorectal cancer: Targeting in imaging and therapyLeukemia Team is aimed to promote personalized medicine by risk-adapted treatment with Acute myeloid leukemia (AML). 1.Establishment of a comprehensive AML database in Taiwan as the backbone for public health promotion and translation researches. 2.Risk stratification of AML patients using integrated prognostic predictors at diagnosis as a therapeutic guide to improve treatment response and decrease side effects. 3.Minimal residual disease (MRD) monitoring after treatment in AML as a guide to optimize clinical management and reduce relapse ratePancreatic Cancer Team: Integration of novel diagnostic and therapeutic tools for improvement of prognosis in pancreatic cancer. 1. Molecular images as a preoperative staging tool and an operative navigator for lymph node dissection in patients with pancreatic cancers. 2. A Novel Non-Thermal Ablation Technique: Irreversible Electroporation Therapy in the Management of Locally Advanced Pancreatic Cancer (LAPCA). 3. Optimization and evaluation of cost-effective screening method for early pancreatic cancer detection program in high risk population. 4. Utilization of biomarkers to develop personalized systemic therapy in advanced pancreatic cancer.Cancer Biomarker Coordinating & Service Center (CBCSC) Core :To integrated the current existing core units and facilities (namely, lab. of dep. of oncology, lab. of molecular diagnostics, molecular lab. of dep. of genetics, translational lab., etc.) of National Taiwan University Hospital (NTUH) and NTU College of Medicine (NTUCM). To develop the determination of novel cancer biomarkers, and serving as coordinating and service center, NTUH. Most biomarkers are qualified through laboratory accreditation (TAF, TAF-PT, etc.), and open for routine service. In the forthcoming years, We will help and support program 1 to 4 to develop the potential novel cancer biomarkers, such as: genomics, proteomics, leukemia, circulating cancer cells, etc.Keywords:Young Female Breast Cancer、Colorectal Cancer、Acute myeloid leukemia (AML)、Pancretic Cancer、Biomarker