ATB – ATB - Applied Tumor Biology, University Hospital Heidelberg

ATB – Applied Tumor Biology

At the Department of Applied Tumor Biology (ATB), we investigate how cancer evolves and interacts with its host, and use this knowledge to develop new strategies for cancer detection, treatment and prevention.

Our research bridges molecular tumor biology, immunology, pathology and computational science. We focus particularly on high-risk settings in which cancer development can be identified and studied before invasive disease occurs, creating unique opportunities for early detection and preventive intervention.

Two complementary models are at the heart of our research: DNA mismatch repair (MMR) deficiency and microsatellite instability (MSI), including Lynch syndrome, and HPV-driven carcinogenesis. While biologically distinct, both provide unique opportunities to study the transition from cancer risk through early molecular and precancerous changes to invasive disease and to develop strategies for early detection, cancer interception and prevention.

HPV-Induced Disease

Human papilloma viruses (HPVs) cause widespread infections of the skin and mucosal surfaces and in some instances pre-cancer and cancer predominantly of the anogenital region and the oropharynx. About 5 % of all cancers that occur worldwide are accountable to persistent HPV-infections.
Research over the past 30 years revealed that the oncogenic activity of HPVs is mediated by two oncogenes (E6 and E7) that are required to induce and maintain their carcinogenic function.
ATB is actively studying the mechanism why these oncogenes become activated in distinct human epithelial cells. ATB further developed biomarkers to highlight such HPV transformed cells and is devloping therapies that block the activity and function of the HPV oncogenes.

OUR APPROACH

MSI Cancers

Every living cell has a set of proteins constituting the DNA Mismatch Repair (MMR) system. The MMR system is responsible for correcting nucleotide mismatches occurring in the DNA during cell replication.

Short repetitive sequences, so-called microsatellites, are particularly prone to accumulation of such mismatches. Therefore, when the MMR system does not function, insertion-deletion mutations accumulate at microsatellites causing Microsatellite Instability (MSI) and leading to cancer development. MSI has dramatic consequences on the pathogenesis and immunogenicity of cancer cells, opening possibilities for immunotherapy and immune prevention of MSI cancers.

OUR APPROACH

Our affiliations: