Identifying new small molecule anti-invasive compounds for glioma treatment.
Glioblastoma is a disease with poor survival rates after diagnosis. Treatment of the disease involves debulking of the tumor, which is limited by the degree of invasiveness of the disease. Therefore, a treatment to halt the invasion of glioma is desirable for clinical implementation. There have been several candidate compounds targeting specific aspects of invasion, including cell adhesions, matrix degradation, and cytoskeletal rearrangement, but they have failed clinically for a variety of reasons. New targets against glioma invasion include upstream mediators of these classical targets in an effort to better inhibit invasion with more specificity for cancer. Included in these treatments is a new class of compounds inhibiting the generation of reactive oxygen species by targeting the NADPH oxidases. These compounds stand to inhibit multiple pathways, including nuclear factor kappa B and Akt. By conducting a screen of compounds thought to inhibit these pathways, a new compound to halt invasion was found that may have a beneficial effect against glioma, based on recent publications. Further, there are still limitations to the treatment of glioblastoma regardless of the discovery of new targets and compounds that should be addressed to better the therapies against this deadly cancer.
Wallace H. Coulter Department of Biomedical Engineering; Georgia Institute of Technology; Atlanta, GA, USA.
Jennifer
J
Munson
Michael
M
Bonner
Levi
L
Fried
Jonathan
J
Hofmekler
Jack
J
Arbiser
Ravi
R
Bellamkonda
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D055808:Drug Discovery; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D054852:Small Molecule Libraries; D019255:NADPH Oxidases; D051057:Proto-Oncogene Proteins c-akt
NADPH oxidase; cancer; drug screen; glioma; invasion