This project responds to one of the topic areas, pediatric brain tumors, directed by Congress. Military personnel, who served in the Iraq and Afghanistan wars, were more likely than our public to be exposed to environmental carcinogens generated from burn pits and transportation fields. Epidemiology studies show that parental exposures to these carcinogens increase the risk of the offspring to develop a brain tumor. Diffuse intrinsic pontine glioma (DIPG) is a form of childhood brain cancer that is aggressive, inoperable, and incurable, with an extremely low 3-year survival rate of 3%. Focal radiotherapy can only prolong the patient survival for a few months. Chemotherapy does not improve the patient survival rate since DIPG is intrinsically resistant to most chemotherapeutics approved by the U.S. Food and Drug Administration. Furthermore, our brains naturally prevent most drugs from reaching the brain tumor. Consequently, DIPG patients and their families and caretakers are held in a stressful and hopeless situation.

The objective of this project is to design a precise, safer, and more effective DIPG treatment. The research will be conducted in a span of 2 years and will be led by three investigators: a neurosurgeon (Mark Souweidane), a pharmaceutical scientist (Benedict Law), and a radiochemist (Richard Ting). Each investigator’s research team has acquired the unique technologies and expertise required to attaining a united goal -- to overcome the treatment and the drug delivery barriers of DIPG. Preclinical studies will be performed using a direct infusion technique, convention-enhanced delivery (CED), to deliver a high regional concentration of a promising targeted combination therapy (panobinostat and GSK-J4) to glioma. The drugs will be incorporated into a novel peptide-derived nanofiber, and administered via CED. The nanofiber will offer a profound benefit of standardizing the delivery of the most effective drug ratio to DIPG, allowing the drugs working together to synergistically eradicate glioma cells. It is expected that using the nanofiber as the drug carrier will prolong the drug-glioma contacting time and increase the treatment duration. This project will also include the investigation of long-term local and systemic CED delivery by imaging. Acquiring such information will lead to the most appropriate dosing schedule for progression to human trial. The current survival rate of DIPG patient is 0%. The proposed studies will lead to a multiplexed approach that potentially can improve the outcome of DIPG treatment and will expect to have a positive clinical impact of improving the patient survival rate.