Evidence-Based Severity Assessment of Animal Models for Pancreatic Cancer

Area of Science:

• Preclinical oncology research
• Animal welfare science
• Veterinary medicine

Background:

• Animal models are essential for cancer research and drug development.
• Adherence to the 3Rs (Replacement, Reduction, Refinement) and EU legislation for animal welfare is mandatory.
• Objective severity assessment is needed to compare different animal models.

Purpose of the Study:

• To establish an objective, data-based severity assessment for murine pancreatic cancer models.
• To compare the severity of orthotopic, subcutaneous, and intravenous pancreatic cancer models.
• To evaluate the utility of the Relative Severity Assessment procedure (RELSA) in animal welfare assessment.

Main Methods:

• Induction of pancreatic cancer in mice via orthotopic, subcutaneous, or intravenous Panc02 cell injection.
• Monitoring of parameters including body weight, distress score, temperature, grimace scale, behavior (burrowing, nesting), and corticosterone levels.
• Application of the Relative Severity Assessment procedure (RELSA) to determine maximum achieved severity (RELSAmax).

Main Results:

• The orthotopic pancreatic cancer model exhibited significantly higher RELSAmax compared to subcutaneous and intravenous models.
• All investigated pancreatic cancer models demonstrated lower severity than models of pancreatitis or bile duct ligation.
• Data-based assessment using RELSA effectively differentiated and compared severity across models.

Conclusions:

• Objective, data-driven assessment provides a valuable tool for evaluating and comparing animal welfare in preclinical cancer models.
• The RELSA procedure offers a standardized method for quantifying animal severity in research.
• Findings support the refinement of animal experiments by enabling informed model selection based on welfare considerations.