Targeting Breast Cancer CNS Metastasis with Oncolytic Polioviruses

摘要

Breast cancer is the most common malignancy in women responsible for > 200,000 new cases/yr in the US. 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 genetics regulatory element that is selectively active in cancer cells but cannot function properly in normal CNS neurons. Our research has documented the relationship of CD1 55 with breast cancer and unraveled the molecular mechanism of cancer specific function of the human rhinovirus internal ribosomal entry site. The prototype oncolytic poliovirus recombinant PVS-RlPO has been manufactured for clinical use and will be introduced into the clinic in 2006. our pre-clinical studies on breast cancer will help to make this treatment available to breast cancer patients.