Document Detail


Targeted toxins for glioblastoma multiforme: pre-clinical studies and clinical implementation.
MedLine Citation:
PMID:  21707497     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Anti-cancer agents in medicinal chemistry     Volume:  11     ISSN:  1875-5992     ISO Abbreviation:  Anticancer Agents Med Chem     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2012-02-08     Completed Date:  2012-10-01     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  101265649     Medline TA:  Anticancer Agents Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  729-38     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain Neoplasms / drug therapy*,  metabolism*
Cell Line, Tumor
Drug Evaluation, Preclinical / methods
Glioblastoma / drug therapy*,  metabolism*
Humans
Immunotoxins / administration & dosage*,  metabolism*
Grant Support
ID/Acronym/Agency:
1 RO1 NS 054193/NS/NINDS NIH HHS; 1F32 NS058156.01/NS/NINDS NIH HHS; 1R01-NS 057711/NS/NINDS NIH HHS; 1R21-NSO54143//PHS HHS; 1UO1 NS052465.01/NS/NINDS NIH HHS; R01 NS 42893/NS/NINDS NIH HHS; R01 NS057711/NS/NINDS NIH HHS; R01 NS057711-05/NS/NINDS NIH HHS; R01 NS074387/NS/NINDS NIH HHS; U01 NS052465/NS/NINDS NIH HHS; U01 NS052465-01A2/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Immunotoxins
Comments/Corrections

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