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Acid ceramidase is a novel drug target for pediatric brain tumors. Oncotarget 2017 Apr 11;8(15):24753-24761

Date

04/28/2017

Pubmed ID

28445970

Pubmed Central ID

PMC5421885

DOI

10.18632/oncotarget.15800

Scopus ID

2-s2.0-85017541087 (requires institutional sign-in at Scopus site)   33 Citations

Abstract

Pediatric brain tumors are the most common solid tumors in children and are also a leading culprit of cancer-related fatalities in children. Pediatric brain tumors remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant levels of acid ceramidase, where levels are highest in the radioresistant tumors, suggesting that acid ceramidase may confer radioresistance. More importantly, we also showed that acid ceramidase inhibitors are highly effective at targeting these pediatric brain tumors with low IC50 values (4.6-50 μM). This data suggests acid ceramidase as a novel drug target for adjuvant pediatric brain tumor therapies. Of these acid ceramidase inhibitors, carmofur has seen clinical use in Japan since 1981 for colorectal cancers and is a promising drug to undergo further animal studies and subsequently a clinical trial as a treatment for pediatric patients with brain tumors.

Author List

Doan NB, Nguyen HS, Montoure A, Al-Gizawiy MM, Mueller WM, Kurpad S, Rand SD, Connelly JM, Chitambar CR, Schmainda KM, Mirza SP

Authors

Mona Al-Gizawiy PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin
Jennifer M. Connelly MD Professor in the Neurology department at Medical College of Wisconsin
Shekar N. Kurpad MD, PhD Sr Associate Dean, Professor in the Neurosurgery department at Medical College of Wisconsin
Wade M. Mueller MD Professor in the Neurosurgery department at Medical College of Wisconsin
Kathleen M. Schmainda PhD Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acid Ceramidase
Animals
Brain Neoplasms
Child
Humans
Mice