Objectives

The long-term objective of this proposal is to increase survival of pancreatic cancer patients by exploring the contribution of the tumour microenvironment to the failure of presently available oncological treatments.

This objective is justified by the following clinical and preclinical observations:

• the failure of cancer-cell targeted medical treatments,
• the presence of a strong desmoplastic reaction in pancreatic cancer and in its preneoplastic conditions and
• the increased risk for the development of cancer in chronic inflammatory diseases of the pancreas.

For this purpose the clinical observation will be reverse-translated into innovative in-vitro and mouse models closely mimicking the human disease. This will allow a profound study of the mechanistic basis of treatment failure by deciphering the complex network between components of the microenvironment and cancer cells leading to increased resistance to chemotherapy and infiltrative growth along adjacent lymphatic and neural structures as well as metastatic spread. Identification of cancer (stem) cell-autonomous as well as stromal-derived mediators of invasion and chemoresistance will lead to novel drug targets to overcome the current therapeutic dilemma.
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Projects and Activities

In order to achieve these overall objectives a work programme has been shaped to systematically dissect the impact of different components of the tumour microenvironment on tumour progression within 5 major experimental work packages (WPs). Each WP is carried out by a varying number of involved parties. The WP leader supervises and adjusts the process flow and works closely with the project office. The activity of the WP is overseen by the chair of the working group.

The titles of these work packages represent the major scientific and technical objectives of this proposal:

• Project Objective A: Targeting the stroma: fibroblastic cells (WP1)
• Project Objective B: Targeting the stroma: inflammatory components (WP2)
• Project Objective C: Targeting the stroma and cancer stem cells to improve treatment response (WP3)
• Project Objective D: Targeting proteases involved in tumour-stroma cross-talk (WP4)
• Project Objective E: Serum markers of stromal biology (WP5)