"Update on molecular mechanisms and novel therapeutic approaches in cholangiocarcinoma" (Prof. Dr. Jens Marquardt)

Prof. Dr. Jens Marquardt of the University Hospital Schleswig-Holstein will visit the M3 Research Center (M3 Research Center, Tübingen, rooms 2.208/209) and give a lecture.

Abstract:
Cholangiocarcinomas (CCA) are highly aggressive malignancies of the biliary tract that encompass a wide spectrum of phenotypically heterogeneous entities. Due to lack of early symptoms, CCA are typically diagnosed in advanced and/or metastatic stages when therapeutic options are limited. Majority of the cases develop on the basis of a chronic inflammatory damage of the liver and/or bile ducts. Thus, the tumor phenotype is defined by molecular heterogeneity that is induced by the combination of driving oncogenes and the type of liver inflammation. The resulting adverse microenvironment creates a pro-oncogenic field effect that ultimately determines the clinical course of individual patients. Notably, the use of immune checkpoint inhibitors (ICI) in combination with chemotherapy has recently been introduced in BTC and led to significant improvement of survival rates. However, molecular biomarkers to select patients likely to benefit form ICI treatments are still missing. Significant advances in molecular-based characterization have further led to the identification of diverse genetic alterations, such as oncogenic mutations in IDH1/2, HER2, KRAS, BRAF or fusions in FGFR2, NTRAK or RET. These alterations are detectable in approx. 30-40% of tumors, can be targeted by next generation inhibitors and confer a dramatic survival benefit compared to conventional chemotherapies. As a result of this significant scientific efforts, CCA is now considered a hallmark for precision medicine approaches in gastro-intestinal oncology and, thus, early molecular testing is mandatory for all cases. However, a sizable number of patients still present without targeted therapeutic options which indicates the imperative need for continuous translational approaches. In addition, we are still lacking defined molecular biomarkers that facilitate response prediction to the majority of available therapies. The talk will summarize clinical progress in the field of CCAs and outline recent advances for the characterization of the cellular composition as well as the interaction between tumor cells and cells within the tumor microenvironment of liver cancer by single cell and spatial approaches that facilitates to improve our understanding of the complex pathophysiology. Further discussion will center on the applicability of these approaches to identify predictive molecular markers to rationalize treatment decisions and/or predict therapeutic resistance. Finally, we will delineate novel treatment strategies for subgroups of CCA patients with undruggable alterations.

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Meeting-ID: 679 8792 8634
Kenncode: 547088