Pancreatic ductal adenocarcinoma (PDAC) causes 34000 deaths in the EU every year. Conventional cancer treatments have close to no impact on this disease. As a result, almost all patients diagnosed with PDAC develop metastases and eventually die. Given this poor outlook, the search for new therapeutics is mandatory. These will have to target relevant cancer pathways and be designed based on the available knowledge on the genetic alterations that characterize this malignancy. We propose to build a team composed of clinicians, translational cancer researchers, chemists, and two pharmaceutical enterprises, to synthesize and implement new drugs for PDAC. The focus of the participants in this project will be on pathways and cellular functions broadly involved in PDAC metastasis and immune escape. These drugs are meant to work through diverse and novel modes of action and will be validated using genetically engineered PDAC mouse models that we have established at the Center for Integrated Oncology in Bonn. By creating and exploring diverse classes of compounds capable of arresting tumor growth and of interfering with its metastatic spread, this project will deliver a high number of new molecules with potential as anticancer therapeutics. In particular, our consortium will produce new indoleamine 2,3-dioxygenase-2 (IDO2) inhibitors, galectin-3 inhibitors, edelfosine analogues, inhibitors of the Hippo signaling pathway, alpha-mannosidase inhibitors, SIRT6 inhibitors, and therapeutics acting by synthetic lethality. For compounds with strong proof-of-concept activity, our consortium will perform the Investigational New Drug (IND)-Enabling Studies, with the goal of delivering a new drug ready to be tested clinically by the end of the project. The PANACREAS project is meant to help find better treatments for PDAC, boost research on this form of cancer in the EU, and open new avenues for scientific and technological innovation.