The Clinical Cooperation Unit Molecular Hematology/Oncology has a basic science focus on causes and consequences of chromosomal instability while its clinical/translational research centers around carcinoma of unknown primary (CUP).

Chromosomal instability is a nearly universal feature of human malignancies and a major contributor to genetic heterogeneity, clonal evolution and metastasis, themselves being at the center of cancer development, progression, relapse, and therapy resistance in solid tumors. One basic research topic focuses on how amplified centrosomes – the spindle pole organizers responsible for correct chromosome segregation during mitosis – lead to chromosomal instability. Specifically, we currently explore whether amplified centrosomes cause tumor formation in a transgenic animal model in vivo. Also, we map the landscape of centrosome aberrations in primary tumor specimens using high resolution 3D electron microscopy approaches.

In CUP syndrome, a paradigm metastatic malignancy in which only metastases but no primary tumor can be identified, we have initiated a large international, randomized phase III trial, examining the role of mutation-based targeted treatments and immunotherapy compared to standard chemotherapy. In addition, we are leading a national multicenter trial to examine the impact of immune checkpoint inhibitor combination therapy in patients with relapsed / refractory CUP syndrome.

Within the frame of these clinical trials and as a synthesis of our basic and clinical research efforts, our translational research program explores the contribution of chromosomal instability to the metastatic process and the poor prognosis of patients with CUP. Overarching goal is the development of novel treatment options in patients with metastatic disease.

The Translational Myeloma Research Group of the Heidelberg Myeloma Center focuses on molecular and pathophysiologic aspects of multiple myeloma, with special interest in mechanisms of drug resistance, spatial heterogeneity of clonal evolution, and novel therapeutic targets. Our group serves as the translational research core of the German-speaking Multiple Myeloma Study Group (GMMG) and is responsible for many correlative science projects in the context of multicenter clinical trials.