title: 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.
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Weidle
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Niewöhner
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Penzberg, Germany georg.tiefenthaler@roche.com.
authors.forename: Georg
authors.initials: G
authors.lastname: Tiefenthaler
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D009362:Neoplasm Metastasis; D054852:Small Molecule Libraries / Q000627:therapeutic use
chemical_list: D054852:Small Molecule Libraries
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