Molecular targeting with recombinant cytotoxins for the treatment of brain tumors

Abstract

AbstractSubstantial progress has been made in the clinical application of molecularly targeted proteinaceous cytotoxins for the treatment of glioblastoma multiforme (GBM), a primary brain tumor of dismal prognosis. These recombinant cytotoxins are composed of tumor‐targeting ligands and genetically engineered derivatives of extremely toxic to eukaryotic cells bacterial toxins. Several cytotoxins moved relatively quickly, as for novel anti‐cancer drugs, from bench to clinic during the last decade; both clinical studies and laboratory research have brought invaluable translational information. The important factors that are linked to the overall cytotoxins' clinical utility are target specificity, proportion of potential responders to a cytotoxin among patients and an efficient delivery of the cytotoxin directly to the tumor site using convection‐enhanced delivery (CED). Novel, potent, and very specific cytotoxins against GBM are being continuously generated. Moreover, a combinatorial targeting of more than one target in GBM with the cytotoxins emerges as an approach of potentially higher anti‐tumor efficacy and more universal usage. Novel means of recombinant cytotoxins delivery are being envisioned and tested. The next decade should bring more complete and successful clinical application of recombinant cytotoxins, a highly promising class of anti‐GBM drugs. Drug Dev Res 69:407–414, 2008. © 2008 Wiley‐Liss, Inc.