The long-term goal of this proposal is to test the efficacy of SapC-DOPS: a unique targeting nanotherapeutic for brain tumors, in combination with chemotherapy. Saposin C (SapC) is a sphingolipid activating protein found ubiquitously throughout the body that functions to catabolize glycosphingolipids. SapC preferentially associates with negatively charged phospholipids at an acidic pH. When SapC is coupled with dioleoylphosphatidylserine (DOPS), stable nanovesicles are formed which can selectively fuse with cancer cells, leading to activation of acid sphingomyelinase and subsequent ceramide accumulation, caspase activation, and eventual apoptosis. In this proposal we seek to investigate any synergistic interactions between SapC-DOPS and chemotherapy, which has broad implications on the future treatment paradigms for glioma and other cancers as well.

Public Health Relevance

The American Cancer Society predicts that there will be 12,740 deaths due to cancers of the brain/nervous system this year. Despite decades of research, survival for patients suffering from glioblastoma remains less than 15 months. Thus, there is an unmet and urgent need to develop new treatment modalities.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31CA171733-01A1
Application #
8526972
Study Section
Special Emphasis Panel (ZRG1-F09-P (21))
Program Officer
Schmidt, Michael K
Project Start
2013-04-03
Project End
2015-04-02
Budget Start
2013-04-03
Budget End
2014-04-02
Support Year
1
Fiscal Year
2013
Total Cost
$30,336
Indirect Cost
Name
Ohio State University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Wojton, Jeffrey; Meisen, Walter Hans; Jacob, Naduparambil K et al. (2014) SapC-DOPS-induced lysosomal cell death synergizes with TMZ in glioblastoma. Oncotarget 5:9703-9
Van Brocklyn, James R; Wojton, Jeffrey; Meisen, Walter H et al. (2014) Aurora-A inhibition offers a novel therapy effective against intracranial glioblastoma. Cancer Res 74:5364-70
Yan, Fengting; Alinari, Lapo; Lustberg, Mark E et al. (2014) Genetic validation of the protein arginine methyltransferase PRMT5 as a candidate therapeutic target in glioblastoma. Cancer Res 74:1752-65