The Blood-Brain Barrier Challenge for the Treatment of Brain Cancer, Secondary Brain Metastases, and Neurological Diseases

Abstract

Formation of metastases from various tumor entities in the brain is a major problem for the treatment of advanced cancer. We describe target molecules and tools for the delivery of small molecules or proteins across the blood-brain barrier (BBB), and the treatment of brain tumors and metastases with antibody-related moieties. In addition, drugs preventing formation of metastases or interfering with the growth of established metastases are described, as well as pre-clinical metastasis models and corresponding clinical data. Furthermore, we discuss the delivery of effector proteins and antibody-based moieties fused with an antibody-based scaffold across the BBB in several model systems which might be applicable for the treatment of brain metastases.

Keywords: Antibody-effector protein fusion; animal metastasis models; antibody–antibody fusion; insulin receptor; molecular Trojan horses; receptor-mediated endocytosis; review; transferrin receptor; tropism of metastasis.