Ben’s Green Drakkoman Fund St. Baldrick’s Research Grant: Evaluation of HER2 inhibition to block metastatic progression in OS Grant uri icon

abstract

  • Osteosarcoma (OS) is the most common primary bone malignancy of children and dogs. The incidence is 8-10 times higher in dogs than in children. Both species share dysregulation of the same pathways that lead to metastasis in over 80% of affected individuals treated with surgery alone. One pathway frequently altered in OS is HER2. This growth factor receptor is well known for the role it plays in aggressive breast cancer in women. However, in OS this protein is located within the cytoplasm rather on the surface of the cells making traditional anti-HER2 therapies like the monoclonal antibody trastuzumab ineffective. Lapatinib (Tykerb®) is a synthetic quinazoline that inhibits HER2 through an intracellular binding site making it a realistic therapeutic option for OS. Lapatinib’s inhibition deactivates downstream pathways activated by HER2 including Ras, Akt and PI3K. In vitro studies against human cell lines have been promising, but to date, no in vivo studies have been published. In this study we aim to investigate the effects of lapatinib on metastatic progression in both species. The ultimate goal of this work is to demonstrate that pet dogs may serve as a relevant preclinical model and to demonstrate the validity of this target across species. (SBFResearch)

date/time interval

  • 2017 - 2019