Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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Targeted Toxins for Glioblastoma Multiforme: Pre-Clinical Studies and Clinical Implementation

Author(s): Marianela Candolfi, Kurt M. Kroeger, Weidong Xiong, Chunyan Liu, Mariana Puntel, Kader Yagiz, AKM Ghulam Muhammad, Yohei Mineharu, David Foulad, Mia Wibowo, Hikmat Assi, Gregory J. Baker, Pedro R. Lowenstein, Maria G. Castro.

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, GBMs 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.

Keywords: IL-13, IL-13Rα2, TGF-α, EGFR, EGFRvIII, pseudomonas exotoxin, diphtheria toxin, gene therapy, targeted toxins

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Article Details

VOLUME: 11
ISSUE: 8
Year: 2011
Page: [729 - 738]
Pages: 10
DOI: 10.2174/187152011797378689
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