Mayo Clinic SPORE in Pancreatic Cancer

胰腺癌马约诊所孢子为致力于降低这种毁灭性恶性肿瘤的发病率和死亡率的转化研究人员建立了最好的环境之一。我们的目标是：1）提供科学的领导和组织，以维持和支持优秀的转化胰腺癌研究; 2）提供组织基础设施，以促进沟通，促进SPORE研究人员和更大的研究社区之间的互动; 3）提供资源，以开发转化胰腺癌研究中的创新研究项目; 4）促进转化胰腺癌研究中的职业发展;和5）通过对SPORE研究计划和项目进行严格的内部审查，并由杰出的外部顾问小组进行定期审查和支持，确保研究的卓越性。在过去的资助期内，在建立基础设施方面取得了巨大进展，促进了创新研究和跨学科互动的开展，并吸引了忠诚的科学家和临床医生。马约诊所每年约有570名胰腺癌患者，占美国所有胰腺癌病例的1.5%。四个核心（行政核心、生物统计核心、临床研究核心和组织核心）将支持SPORE的研究。对研究人员和研究基础设施的广泛机构支持将有助于将科学发现转化为患者。项目1，GSK-3对胰腺癌细胞增殖和存活的调节（由Billadeau和Kim博士领导）将研究GSK-3 P如何在胰腺癌中过度表达，评估其作为小鼠模型中的新型化疗靶点，并研究GSK-3抑制剂在患者中的作用。项目2，胰腺癌相关糖尿病（PaCDM）：发病机制和生物标志物（由Chari和Klee博士领导）将检查B细胞功能障碍是否是PaCDM的早期缺陷，确定肾上腺髓质素是否是PaCDM的介导者：并开发和验证新发糖尿病患者中PaC的预测模型。项目3，Hedgehog和EGF途径相互作用：胰腺癌多靶点治疗的新方法（由Fernando-Zapico和Erlichman博士领导）将研究HH-EGF途径相互作用的机制;确定对HH-EGF联合治疗的反应与新的成像标记物，并进行I/II期试验。项目4，开发直接输送至胰腺肿瘤部位的免疫调节疗法（由Mukherjee和Alberts博士领导）将在PDA.MUC1 Tg小鼠中优化基于MUC 1的疫苗;评估胰腺癌患者的免疫状态，以确定在PDA小鼠中观察到的免疫耐受和监视机制是否与人类患者相似;并利用基于MUC 1肽的疫苗进行I期试验。总之，这种竞争性的更新申请将继续我们在促进胰腺癌转化研究方面的强大轨迹。

The Mayo Clinic SPORE in Pancreatic Cancer has built one of the best environments for translational researchers who are committed to the goal of reducing the incidence and mortality of this devastating malignancy. Our aims are to: 1) Provide the scientific leadership and organization to sustain and support outstanding translational pancreatic cancer research; 2) Provide the organizational infrastructure to facilitate communication and promote interactions among SPORE investigators and the larger research community; 3) Provide resources to develop innovative research projects in translational pancreatic cancer research; 4) Foster career development in translational pancreatic cancer research; and 5) Assure excellence of research through a rigorous internal review process of the SPORE research programs and projects, with periodic review and support from a panel of outstanding external advisors. Over the past funding period, tremendous progress has been made in creating an infrastructure that nurtures the conduct of innovative research and interdisciplinary interactions, and which has attracted committed scientists and clinicians. Mayo Clinic sees -570 patients with pancreatic cancer annually, constituting 1.5% of all pancreatic cancer cases in the U.S. Four cores (Administrative Core, Biostatistics Core, Clinical Research Core, and Tissue Core) will support research in the SPORE. Broad institutional support for investigators and the research infrastructure will facilitate the translation of scientific discovery to the patient. Project 1, Regulation of Pancreatic Cancer Cell Proliferation and Survival by GSK-3 (led by Drs. Billadeau & Kim) will study how GSK-3P is over-expressed in pancreatic cancer, evaluate it as a novel chemotherapeutic target in mouse models, and study a GSK-3 inhibitor in patients. Project 2, Pancreatic Cancer-associated Diabetes (PaCDM): Pathogenesis and Biomarkers (led by Drs. Chari & Klee) will examine if B-cell dysfunction is an early defect in PaCDM, determine if adrenomedullin is the mediator of PaCDM: and develop and validate a predictive model for PaC among new-onset diabetics. Project 3, Hedgehog and EGF Pathway Interaction: A Novel Approach For A Multi-Target Therapy in Pancreatic Cancer (led by Drs. Fernandez-Zapico & Erlichman) will study the mechanisms underlying the HH-EGF pathway interaction; determine response to HH-EGF combined therapy with new imaging markers, and perform a phase l/ll trial. Project 4, Development of Immune-Modulating Therapies Delivered Directly to the Pancreatic Tumor Site (led by Drs. Mukherjee & Alberts) will optimize a MUC1-based vaccine in the PDA.MUC1 Tg mouse; assess immune status of pancreatic cancer patients to determine if the immune tolerance and surveillance mechanisms observed in the PDA mouse appropriately resemble human patients; and conduct a Phase I trial utilizing a MUC1-peptide based vaccine. In summary, this competing renewal application will continue our strong trajectory of facilitating translational research in pancreatic cancer.