Robust scoring system to evaluate animal well-being in murine orthotopic breast cancer and ovarian cancer models
Orthotopic models are critical to the development of new cancer therapies, as they have the greatest potential to mimic human cancer progression. However, orthotopic models are often underutilized due to practical challenges. These challenges include the need for specialized surgeries and the presence of complicating symptoms, such as ascites fluid accumulation in ovarian cancer and liver disease models, as well as ulceration of breast tumors growing in the mammary fat pad. An adaptable, quantitative animal health assessment system that utilizes simple, non-invasive, visual measurements can allow researchers to use these models to their full potential while safeguarding humane endpoints. The goal of this work was to establish such health scoring systems for translationally-relevant ovarian (ID8 Defb29-Vegf-A) and breast cancer (triple-negative model 4T1) models. We developed a tractable health assessment system by monitoring a combination of activity and responsiveness, coat condition, respiratory function, changes in body weight, posture, gait, tumor size (where measurable), and extent of ulceration, and scoring each of these parameters using a simple numerical scale. The scores at which euthanasia or other interventions were required were estimated and then adjusted based on clinical assessment by a team of researchers and veterinarians. These semi-quantitative health scoring systems were applied to survival experiments, in which mice were euthanized at a predetermined score or upon meeting a superseding health criterion, to confirm their applicability and effectiveness in maintaining humane endpoints. The scoring systems presented are intended to build on previously-established generic tumor model scoring systems that do not accommodate for the particular phenotypes present in orthotopic breast and ovarian cancer models.