Targeted Toxins for Glioblastoma Multiforme: pre-clinical studies and clinical implementation

CANDOLFI; KROEGER; XIONG; LIU; PUNTEL; YAGIZ; MUHAMMAD; MINEHARU; FOULAD; WIBOWO; ASSI; BAKER; LOWENSTEIN; CASTRO

ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2011 vol. 11 p. 729 - 738

1871-5206

Glioblastoma multiforme (GBM) is most common primary brain tumor in adults. GBM is veryaggressive due to its poor cellular differentiation and invasiveness, which makes complete surgicalresection virtually impossible. Therefore, GBM’s invasive nature as well as its intrinsic resistanceto current treatment modalities makes it a unique therapeutic challenge. Extensive examination ofhuman GBM specimens has uncovered that these tumors overexpress a variety of receptors thatare virtually absent in the surrounding non-neoplastic brain. Human GBMs overexpress receptorsfor cytokines, growth factors, ephrins, urokinase-type plasminogen activator (uPA), andtransferrin, which can be targeted with high specificity by linking their ligands with highlycytotoxic molecules, such as Diptheria toxin and Pseudomonas exotoxin A. We review thepreclinical development and clinical translation of targeted toxins for GBM. In view of the clinicalexperience, we conclude that although these are very promising therapeutic modalities for GBMpatients, efforts should be focused on improving the delivery systems utilized in order to achievebetter distribution of the immuno-toxins in the tumor/resection cavity. Delivery of targeted toxinsusing viral vectors would also benefit enormously from improved strategies for local delivery.