DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Targeting Breast Cancer CNS Metastasis with Oncolytic Polioviruses

Principal Investigator: GROMEIER, MATTHIAS
Institution Receiving Award: DUKE UNIVERSITY
Program: BCRP
Proposal Number: BC033115
Award Number: W81XWH-04-1-0644
Funding Mechanism: Concept Award
Partnering Awards:
Award Amount: $115,500.00


PUBLIC ABSTRACT

Breast cancer is the most common malignancy in women, responsible for more than 200,000 new cases per year in the United States. Early detection and surgical/radiation therapy can eliminate cancerous growths, but in many cases, late complications result in metastatic spread frequently involving the central nervous system (CNS). There are currently no effective treatments for CNS metastasis of breast cancer, and therefore, this condition is almost invariably fatal.

We have developed a new cancer treatment strategy specifically tailored to target and destroy malignant tumors arising in the CNS. Our treatment is based on poliovirus that we have genetically manipulated to eliminate its disease-causing properties. Poliovirus naturally targets a cellular protein named CD155, which is normally expressed in CNS motor neurons. However, we discovered that CD155 is abnormally expressed in many cancer cells, including breast cancer. We have made poliovirus clinically applicable by manipulating a crucial genetic regulatory element that is selectively active in cancer cells but cannot function properly in normal CNS neurons.

Our research will investigate (1) the precise expression levels and distribution of the poliovirus receptor CD155 in breast cancers and secondary CNS metastasis and (2) the mechanism of selective viral gene expression in breast cancer cells. Since the CD155 receptor provides a target for cancer-fighting polioviruses, diagnostic tests to evaluate its distribution are critical to identify patients and tumor types most likely to respond to the treatment.