SFB 1321: Modelling and Targeting Pancreatic Cancer

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。一个几乎普遍致命的结果，缺乏进展的治疗靶向和不断上升的发病率强调了巨大的医疗和社会经济需求与这种癌症实体。CRC 1321开始设计新的途径，PDAC靶向通过推进我们的机械理解其生物学。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）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，产生了重要的知识。除其他外，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，这些都推动了CRC的创新和发现，因此慕尼黑现在是国际公认的胰腺癌研究的主要欧洲中心。对于第二个资助期，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额外专家来进一步发展CRC。我们将扩大我们的努力，通过整体的方法来询问疾病的独特生物学特征，以解开其侵略性和治疗抗性的分子，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研究过程，这将通过尖端遗传工具，筛选方法和分析专业知识的S项目得到支持。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，以绘制脆弱性景观和燃料假设生成和创新。虽然机械研究将继续是CRC的核心，但一些项目也将进入一个更具转化性的阶段。用于翻译的技术、模型和实验平台，如药物筛选、抗体工程和跨三个物种的先进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%的癌症研究资金用于PDAC。CRC1321是一项国际知名的倡议，汇集了30个项目负责人，通过高度综合的研究计划研究一种疾病。

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.