SFB 1321: Modelling and Targeting Pancreatic Cancer

SFB 1321：胰腺癌建模和靶向治疗

• 批准号: 329628492
• 金额: --
• 依托单位: Ludwig-Maximilians-Universität München (LMU)
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/329628492?language=en
• 关键词: SFB; 1321; Modelling; Targeting; Pancreatic

Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer related death in the western world and predicted to become second in due course. An almost universally fatal outcome, lacking advances in therapeutic targeting and rising incidences underline the enormous medical and socioeconomic needs associated with this cancer entity.The CRC1321 set out to devise new avenues for PDAC targeting through advancing our mechanistic understanding of its biology. To address major challenges in the field, we brought together interdisciplinary expertise ranging from cancer biology, immunology, (epi)genomics, metabolomics and proteomics to disease modelling, computational and translational sciences. Through intense collaborations, CRC scientists crossed borders and generated important knowledge. Among others, the discoveries shed light on the molecular mechanisms of cellular plasticity and metastasis, uncovered features of the tumor-suppressive microenvironment, described molecular principles of PDAC related thrombosis and cachexia, and developed new therapeutic strategies that are currently being investigated in clinical studies. We also made major contributions to the field through the development of disease models, technology and methods for PDAC research, which are fueling innovations and discoveries in the CRC, and for which Munich is now internationally recognized as a major European hub for pancreatic cancer research.For the second funding period, we propose to develop the CRC further by recruiting additional expertise that ranges from bioengineering and biophysics to developmental and stem cell biology. We will expand our efforts to interrogate the disease´s unique biological features through a holistic approach, to unravel the molecular, cellular, micro- and macroenvironmental underpinnings of its aggressiveness and therapy resistance. CRC scientists will increasingly study processes using scalable functional genomic approaches, which will be supported through the S projects by cutting-edge genetic tools, screening methods and analytical expertise. The molecular characterization of our PDAC cell atlas, which we initiated in the first funding period, will be expanded by additional molecular and functional layers to map vulnerability landscapes and fuel hypothesis generation and innovation. Whilst mechanistic studies will continue to be at the core of the CRC, a number of projects will also advance to a more translational stage. Technologies, models and experimental platforms for translation, such as drug screening, antibody engineering and advanced PDAC models across three species will facilitate these efforts. PDAC is one of the biggest challenges in cancer care. Yet, only 2% of cancer research funding in the European Union is dedicated to PDAC. CRC1321 is an internationally visible initiative that brings together 30 project leaders to study one disease through a highly integrative research program.

胰腺导管腺癌（PDAC）是西方世界癌症相关死亡的第三大原因，预计在适当的时候将成为第二大原因。几乎普遍致命的结果、治疗靶向方面缺乏进展以及发病率不断上升，凸显了与这种癌症实体相关的巨大医疗和社会经济需求。CRC1321 着手通过推进我们对其生物学的机制理解，为 PDAC 靶向设计新途径。为了应对该领域的重大挑战，我们汇集了从癌症生物学、免疫学、（表观）基因组学、代谢组学和蛋白质组学到疾病建模、计算和转化科学的跨学科专业知识。通过密切合作，CRC 科学家跨越国界并产生了重要的知识。其中，这些发现揭示了细胞可塑性和转移的分子机制，揭示了肿瘤抑制微环境的特征，描述了PDAC相关血栓形成和恶病质的分子原理，并开发了目前正在临床研究中研究的新治疗策略。我们还通过开发用于 PDAC 研究的疾病模型、技术和方法，为该领域做出了重大贡献，这推动了 CRC 的创新和发现，慕尼黑现在被国际公认为欧洲主要的胰腺癌研究中心。在第二个资助期，我们建议通过招募从生物工程和生物物理学到发育和干细胞生物学的更多专业知识来进一步发展 CRC。我们将加大努力，通过整体方法探究该疾病独特的生物学特征，以揭示其侵袭性和治疗耐药性的分子、细胞、微观和宏观环境基础。 CRC 科学家将越来越多地使用可扩展的功能基因组方法来研究过程，这些方法将通过 S 项目得到尖端遗传工具、筛选方法和分析专业知识的支持。我们在第一个资助期启动的 PDAC 细胞图谱的分子表征将通过额外的分子和功能层进行扩展，以绘制脆弱性图谱并促进假设的生成和创新。虽然机制研究将继续成为 CRC 的核心，但许多项目也将进入转化阶段。翻译技术、模型和实验平台，例如跨三个物种的药物筛选、抗体工程和先进的 PDAC 模型，将促进这些努力。 PDAC 是癌症治疗中最大的挑战之一。然而，欧盟只有 2% 的癌症研究资金专门用于 PDAC。 CRC1321 是一项国际知名的倡议，汇集了 30 名项目负责人，通过高度综合的研究计划来研究一种疾病。