New insights into affinity proteins for HER2-targeted therapy: Beyond trastuzumab

Human epidermal growth factor receptor 2 (HER2) is known as a potential target for both cancer treatment and diagnosis. One of the most interesting HER2-targeted therapeutics is an affinity protein which selectively recognizes and binds to a defined target. Trastuzumab is a monoclonal antibody which has been approved as the first affinity proteins for treatment of some HER2-positive cancers including breast cancer. Despite initial response to trastuzumab, the majority of patients with metastatic HER2-positive breast cancer still show resistance to the therapy. Recently, various anti-HER2 affinity proteins, including antibodies, antibody fragments (e.g., Fab and scFv) and other protein scaffolds (e.g., affibody and DARPin), alone or fused/conjugated with therapeutic agents (e.g., proteins, drugs and radioisotopes) have been developed to overcome the trastuzumab resistance. Here, we review these engineered affinity proteins which are either clinically approved or under evaluation. Modern technologies and future prospects for their clinical applications in cancer treatment are also discussed.