NEO 212 Enhances Temozolomide's Ability To Increase Radiosensitivity And Cytotoxicity In Glioblastoma Tumors

Developing A Clinically Relevant Radiosensitizer For Temozolomide-Resistant Gliomas.

Authors: Radu O. Minea¹, Tuan Cao Duc², Stephen D. Swenson¹, Hee-Yeon Cho¹, Mickey Huang³, Hannah Hartman⁴, Florence M. Hofman⁵, Axel H. Schonthal⁴and Thomas C. Chen^1,5

A new study into the effectiveness of NEO 212, a conjugate formulation of Temozolomide (TMZ) and Peryllil Alcohol (POH) designed for internasal delivery, to enhance the ability of (TMZ) to slow or stop the formation of Glioblastoma Tumors demonstrates additional benefits over TMZ treatment alone. 

For those with Glioblastoma (GB) brain cancer, the survival prognosis is low. TMZ remains one of the gold standards in the treatment of GB to extend the overall median survival of patients. One of the mechanisms that TMZ provides is the ability to increase the radiosensitization or sensitivity of the tumor, to the lethal effects of radiation therapy done in conjunction with TMZ. This benefit though is greatly minimized in tumors expressing O6-methylguanine DNA methyltransferase (MGMT) as TMZ alone at clinical concentrations is not potent enough to overcome MGMT expression.

With NEO 212, TMZ can be delivered directly to the tumor site intranasally thereby bypassing the blood-brain barrier at a higher concentration level resulting in greater tumor cell uptake. This study demonstrates in vitro NEO 212 delivery to GB cell lines, including TMZ-resistant isogenic variants, revealed more potent cytotoxic and radiosensitizing activities at physiologic concentrations.

¹ Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, ² Haiphong University School of Pharmacy, Haiphong, Vietnam, ³ Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA, USA, ⁴Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, ⁵Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA