Proof-of-Concept Study of an Alpha-Fetoprotein-Derived Peptide for the Management of Canine Mammary Cancer

SIMPLE SUMMARY: Dogs needing treatment in addition to surgery for the management of mammary cancer should be given something that is not foreign to their system and that is well-tolerated and effective. Many canine mammary cancers are promoted in their growth by estrogen. Alpha-fetoprotein (AFP) is a mammalian protein that has anti-estrogenic properties. The anti-estrogenic site of AFP was isolated and developed into a drug referred to as AFPep. AFPep inhibited the development and growth of mammary cancers in rodents. The purpose of the study reported herein was to determine the tolerability of AFPep in normal and tumor-bearing dogs. Blood levels of AFPep, previously shown to inhibit mammary cancer growth in rodents, were achieved in dogs by injection as well as by the oral route of drug administration. In all cases, AFPep was well tolerated in dogs, as assessed by clinical behaviors as well as comprehensive blood tests. The data indicate that AFPep should be further developed for use against mammary cancer in dogs. ABSTRACT: Novel, well-tolerated drugs are needed for the management of canine mammary cancer. Many of these cancers are promoted in their growth by estrogen. Alpha-fetoprotein (AFP) is a ubiquitous mammalian protein that has anti-estrogenic properties. AFPep (the anti-estrogenic site of AFP) has been developed into a readily synthesizable drug. AFPep has been shown to have anti-mammary cancer activity in several models of this disease, both in cell culture and in rodents. The purpose of the study reported herein was to determine the tolerability of AFPep in normal and tumor-bearing dogs. AFPep was given to dogs via both parenteral and oral routes in a single application and in repeated daily doses. Full clinical chemistry and hematology values were determined before and after drug administration. Blood levels of the drug were achieved in dogs that had been previously found to be oncostatic in rodents. No changes in clinical chemistry, hematology, and clinical behaviors were found in dogs following drug administration. The data support the further development of AFPep for clinical use against canine mammary cancer.