Mechanisms of Evasive Resistance in Cancer

Cancer is a major health problem, but current cancer therapies fail to effectively eliminate the disease. The RTD Project MERIC now aims to find out how tumor cells change their signaling pathways to escape treatment.

Extensive research over decades has led to the development of therapies that target cancer-specific signaling pathways. Tumors can however escape such therapies by activating compensatory signaling pathways, a process referred to as "evasive resistance". The identities of the alternative signaling pathways and the functional interconnections that underlie evasive resistance remain widely unknown. Elucidating their mechanisms is currently a major challenge in cancer research.

Shedding light on the mechanism of evasive resistance

To understand the changes in the signaling pathways that enable tumors to evade therapy, the scientists working on the RTD Project MERIC will integrate cutting-edge clinical, computational, and molecular approaches. With the help of rigorously designed clinical studies, the scientists will be able to work with diseased tissue isolated before therapy, during treatment, and at the time of tumor progression.

The tissue, chosen based on medical importance, accessibility to repeated sampling, and ethical considerations, will come from hepatocellular carcinoma (HCC). The biomedical scientists and computational biologists in the team will apply high- and low-throughput experimental and computational methods to determine, characterize, and model the underlying signaling defects that allow tumors to circumvent therapy.

Following cellular signaling changes of cancer cells over time

This research process will be iterative, meaning that the researchers will monitor changes in treatment strategies several times in the same patient or experimental model. This way, they will be able to follow the individual changes in cell signaling of the respective tumors, and track the influence of the medication.

Once the molecular pathomechanisms in oncogenesis are revealed, the interdisciplinary MERIC team plans to identify new drug targets and predictive biomarkers. In doing so, they hope to contribute to the rational design of personalized medicine approaches by increasing therapeutic efficacy and reducing side effects and the financial burden of treatment for the benefit of the patient.