Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of malignant pancreatic cancers and is now the fourth most common cause of cancer-related deaths in the western world. Despite advances in tumour detection and treatment, pancreatic cancer remains one of the deadliest malignancies with a 5-year survival rate of less than 10%. The poor prognosis of pancreatic cancer is due to a low early detection rate, rapid progression, the development of drug resistance and the lack of an effective therapy. The only potentially curative option is surgical resection of the tumour, although only around 20 % of patients have a surgically resectable tumour. The molecular mechanisms of therapy resistance in pancreatic carcinoma are not yet fully understood, but are based in particular on genetic and epigenetic changes that lead, among other things, to a dense and immunosuppressive tumour microenvironment. In this project, we are focusing in particular on the cellular and molecular biological relationships between changes in matrix proteins in the tumour microenvironment and the development of immune and chemotherapy resistance. These findings enable new diagnostic strategies to predict resistance mechanisms in pancreatic cancer and to break through them with innovative approaches.

Cancer of the upper GI tract (GI-CA) and the hepatic-pancreatic-biliary system (HPB-CA) typically has a poor prognosis, especially as most of these tumours are only diagnosed at a very advanced tumour stage. In addition, HPB-CA has a pronounced pre-existing and/or acquired resistance to therapy. Innovative approaches aimed at improving diagnosis and screening as well as developing personalised therapy strategies are therefore urgently needed.

Cancer liquid biopsy, i.e. the diagnosis of body fluids instead of tumour tissue samples, offers promising opportunities for broad-based and cost-effective screening in cancer prevention. The focus here is on the analysis of circulating tumour cells, cell-free nucleic acids and exosmoses. Nevertheless, liquid biopsy is not yet a widely established standard procedure.

In personalised cancer therapy, treatment is tailored to the specific tumour characteristics, e.g. the nature of the tumour microenvironment, the immune status of the tumour or resistance to therapy. Tumour organoids, which reflect the cellular and molecular heterogeneity of a tumour very well, are developing into a promising diagnostic platform in this context.

By combining liquid biopsy and organoid-based therapeutic tests, we aim to achieve a significant improvement in tumour diagnostics and establish interdisciplinary (chemotherapy, radiotherapy and surgery) personalised therapeutic strategies.

Colorectal carcinoma is one of the most common types of cancer worldwide. Approximately one million new tumours and 500,000 deaths per year highlight the urgent need to find new therapeutic approaches in the fight against colorectal carcinoma. Based on the TNM classification, tumours are classified according to their tumour size, lymphogenic metastasis and distant metastases. The classification results in a prognosis assessment and treatment recommendation. Conventional therapy involves surgical removal of the tumour and various chemotherapy regimes.

Immunopathological and matrix-altering mechanisms play a role in the development, progression and metastasis of the tumour. In this context, the role of regulatory microRNAs (miRNA) is an interesting field of research.

miRNAs act as negative regulators of gene expression and are involved in the regulation of biological processes, including cell growth, differentiation and apoptosis, both under physiological conditions and in diseases such as tumours.

In this project, we investigate the molecular regulatory mechanisms of angiogenic and fibrosis-associated microRNAs in tumourigenesis, progression and metastasis in colorectal carcinoma.

In particular, we analyse correlations between the expression of individual microRNAs and the classical histopathological TNM categories and patient survival. The knowledge gained from this enables the development of new treatment strategies for recurrent colorectal carcinoma.