Models useful in determining whether fibroblast growth factor 19 variant polypeptides having glucose-lowering activity and/or anti-obesity activity also exhibit favorable oncology-related profiles, and methods and uses associated therewith. Also provided are methods of antagonizing the oncogenic activity of FGF19 in a subject and, in certain embodiments, methods of preventing or treating a disease, disorder or condition, such as a FGF19-dependent disease, disorder or condition, or a symptom thereof.