Nano Drug Crosses Blood-Brain Tumor Barrier
News Jul 22, 2013
An experimental drug in early development for aggressive brain tumors can cross the blood-brain tumor barrier, kill tumor cells and block the growth of tumor blood vessels, according to a study led by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
The laboratory and animal study also shows how the agent, called SapC-DOPS, targets tumor cells and blood vessels. The findings support further development of the drug as a novel treatment for brain tumors.
Glioblastoma multiforme is the most common and aggressive form of brain cancer, with a median survival of about 15 months. A major obstacle to improving treatment for the 3,470 cases of the disease expected in the United States this year is the blood-brain barrier, the name given to the tight fit of cells that make up the blood vessels in the brain. That barrier protects the brain from toxins in the blood but also keeps drugs in the bloodstream from reaching brain tumors.
“Few drugs have the capacity to cross the tumor blood-brain barrier and specifically target tumor cells,” says principal investigator Balveen Kaur, PhD, associate professor of neurological surgery and chief of the Dardinger Laboratory of Neurosciences at the OSUCCC – James. “Our preclinical study indicates that SapC-DOPS does both and inhibits the growth of new tumor blood vessels, suggesting that this agent could one day be an important treatment for glioblastoma and other solid tumors.”
The findings were published in a recent issue of the journal Molecular Therapy.
SapC-DOPS (saposin-C dioleoylphosphatidylserine), is a nanovesicle drug that has shown activity in glioblastoma, pancreatic cancer and other solid tumors in preclinical studies. The nanovesicles fuse with tumor cells, causing them to self-destruct by apoptosis.
Key findings of the study, which used two brain-tumor models, include:
• SapC-DOPS binds with exposed patches of the phospholipid phosphatidylserine (PtdSer) on the surface of tumor cells;
• Blocking PtdSer on cells inhibited tumor targeting;
• SapC-DOPS strongly inhibited brain-tumor blood-vessel growth in cell and animal models, probably because these cells also have high levels of exposed PtdSer.
• Hypoxic cells were sensitized to killing by SapC-DOPS.
“Based on our findings, we speculate that SapC-DOPS could have a synergistic effect when combined with chemotherapy or radiation therapy, both of which are known to increase the levels of exposed PtdSer on cancer cells,” Kaur says.
Other researchers involved in this study were Jeffrey Wojton, Haritha Mathsyaraja, Walter H. Meisen, Nicholas Denton, Chang-Hyuk Kwon and Michael C. Ostrowski of The Ohio State University; and Zhengtao Chu, Lionel M.L. Chow, Mary Palascak, Robert Franco, Tristan Bourdeau, Sherry Thornton and Xiaoyang Qi of the University of Cincinnati.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only four centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 228-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S.News & World Report.
CRISPR Reveals New Targets for Promising Cancer DrugsNews
Novel screening method identifies new drug targets that could potentially enhance the effectiveness of PD-1 checkpoint inhibitors, a promising new class of cancer immunotherapy.READ MORE
Cell Recycling System Offers Therapeutic Entry Point for Rare Disease TreatmentNews
Scientists have demonstrated how an investigational drug works against a rare, fatal genetic disease, Niemann-Pick type C1 (NPC1).READ MORE
UK Not Ready for Brexit’s Impact on Food, Report WarnsNews
Severe problems with the UK food system are likely unless issues are addressed, according to latest expert reportREAD MORE
Comments | 0 ADD COMMENT
EMBL Conference: European Conference of Life Science Funders and Foundations
Apr 19 - Apr 20, 2018
EMBL Course: Techniques for Mammary Gland Research
Mar 05 - Mar 09, 2018
EMBL Course: Target Engagement in Biology and Drug Discovery
Feb 19 - Feb 23, 2018