Refinement of preclincal cancer research

• Applicant: Dr. Simone Kumstel
• Subject Area: Veterinary Medical Science ; Hematology, Oncology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465123540

During recent decades, a continuous improvement of animal experiments has been demanded by the general public. A possible approach is to reduce pain, suffering and distress of the animals through animal model-specific refinement. In translational and applied research, most of the laboratory animals are used for preclinical oncological studies. The distress for these animal models in particular should be reduced to an absolute minimum, since stress has been shown to influence tumor progression and might therefore be a confounding factor for preclinical studies. To facilitate comparable refinement of animal models, a detailed assessment of distress will be carried out using different cell-based implantation models and genetically induced mice models for pancreatic and colorectal carcinoma. For this purpose, well-established parameters, such as burrowing activity, nest building behavior, body weight, distress score, body temperature and corticosterone concentration in plasma or corticosterone metabolites in feces will be evaluated during cancer progression. By analyzing these parameters with multivariate mathematical methods, we will characterize early humane endpoints, which correlate directly with distress and survival. To verify the predictive evidence of the early humane endpoints under chemotherapy of these tumors an innovative combinatorial treatment with c-Raf and EGFR-inhibitors will be tested. Side effects of the drugs will also be evaluated by detailed assessment of distress. Additionally, different analgesics (metamizol, tramadol, buphrenophine) will be analyzed with focus on their analgesic efficacy and their possible influence on tumor progression, to facilitate an optimal pain release in the oncological animal models. Therefore, we will use additional parameters, such as telemetric monitoring of activity, body temperature and heart rate, as well as the mouse grimace scale. By using the established refinement strategies of this research project, pain and distress of laboratory animals should be sustainably reduced to facilitate oncological in vivo research with high animal welfare standards in future.

• DFG Programme: Research Grants