title: Targeted toxins for glioblastoma multiforme: pre-clinical studies and clinical implementation.
abstract: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. GBM is very aggressive due to its poor cellular differentiation and invasiveness, which makes complete surgical resection virtually impossible. Therefore, GBM's invasive nature as well as its intrinsic resistance to current treatment modalities makes it a unique therapeutic challenge. Extensive examination of human GBM specimens has uncovered that these tumors overexpress a variety of receptors that are virtually absent in the surrounding non-neoplastic brain. Human GBMs overexpress receptors for cytokines, growth factors, ephrins, urokinase-type plasminogen activator (uPA), and transferrin, which can be targeted with high specificity by linking their ligands with highly cytotoxic molecules, such as Diptheria toxin and Pseudomonas exotoxin A. We review the preclinical development and clinical translation of targeted toxins for GBM. In view of the clinical experience, we conclude that although these are very promising therapeutic modalities for GBM patients, efforts should be focused on improving the delivery systems utilized in order to achieve better distribution of the immuno-toxins in the tumor/resection cavity. Delivery of targeted toxins using viral vectors would also benefit enormously from improved strategies for local delivery.
authors.affiliation: Department of Neurosurgery, Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109-0650, USA.
authors.forename: Marianela
authors.initials: M
authors.lastname: Candolfi
authors.forename: Kurt M
authors.initials: KM
authors.lastname: Kroeger
authors.forename: Weidong
authors.initials: W
authors.lastname: Xiong
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.forename: Mariana
authors.initials: M
authors.lastname: Puntel
authors.forename: Kader
authors.initials: K
authors.lastname: Yagiz
authors.forename: Akm Ghulam
authors.initials: AG
authors.lastname: Muhammad
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mineharu
authors.forename: David
authors.initials: D
authors.lastname: Foulad
authors.forename: Mia
authors.initials: M
authors.lastname: Wibowo
authors.forename: Hikmat
authors.initials: H
authors.lastname: Assi
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Baker
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Lowenstein
authors.forename: Maria G
authors.initials: MG
authors.lastname: Castro
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000378:metabolism*
chemical_list: D000922:Immunotoxins