Mayo Clinic SPORE in Pancreatic Cancer

胰腺癌的梅奥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翻译研究人员建立了最佳环境之一。我们的目标是：1)提供科学领导和组织，以支持和支持杰出的胰腺癌转化性研究；2)提供组织基础设施，以促进孢子研究人员和更大的研究社区之间的沟通和互动；3)提供资源，开发胰腺癌转化性研究的创新研究项目；4)促进胰腺癌转化性研究的职业发展；以及5)通过对孢子研究计划和项目的严格内部审查过程，以及由一组杰出的外部顾问的定期审查和支持，确保研究的卓越。在过去的资助期间，在建立促进创新研究和跨学科互动的基础设施方面取得了巨大进展，并吸引了坚定的科学家和临床医生。梅奥诊所每年有570名胰腺癌患者，占美国所有胰腺癌病例的1.5%。四个核心(管理核心、生物统计核心、临床研究核心和组织核心)将支持对该孢子的研究。对调查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-3P如何在胰腺癌中过度表达，在小鼠模型中评估其作为新的化疗靶点的作用，并在患者中研究GSK-3抑制剂。项目2，胰腺癌相关糖尿病(PaCDM)：发病机制和生物标记物(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的介质：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通路相互作用：胰腺癌多靶点治疗的新方法(由Fernandez-Zapico和Erlichman博士领导)将研究HH-EGF途径相互作用的潜在机制；使用新的成像标记物确定HH-EGF联合治疗的疗效，并进行L/111期试验。项目4，直接注射到胰腺肿瘤部位的免疫调节疗法的开发(由Mukherjee和Alberts博士领导)将在PDA MUC1TG小鼠身上优化基于MUC1的疫苗；评估胰腺癌患者的免疫状态，以确定在PDA小鼠身上观察到的免疫耐受和监测机制是否与人类患者适当相似；以及利用MUC1多肽疫苗进行I期试验。总而言之，这一竞争性的更新申请将继续我们促进胰腺癌翻译研究的强劲轨迹。

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.