CHLORIDE CHANNELS: NOVEL TARGETS FOR CANCER TREATMENT

Summary

Principal Investigator: Susan Lyons
Abstract: The prognosis for highly invasive peripheral neuroectodermal tumors (PNETs) is discouraging with the current standard of care treatments. We have discovered that (1) a novel chloride channel (GCC) exists on the cell surface of glioma cells, but not normal brain cells and (2) chlorotoxin (Cltx), a scorpion venom toxin, binds to all grades of primary brain tumors collectively called gliomas. Cltx targets and tightly binds specifically to GCC on glioma cells. Since gliomas share a common tissue origin with PNETs, we predicted that they may share common cell- surface antigens that act as markers. Our preliminary histochemical staining results with Cltx suggest that GCC appears to be a tumor- specific antigen found not only on gliomas, but also PNETs. The Company has developed a "biological smart missile" using Cltx as the guidance system to target radioactive isotopes, cytolytic molecules, or cytotoxic chemicals to GCC on glioma cells. We propose to (1) confirm our preliminary observations on the presence of GCC on PNETS and (2) develop a GCC-targeted cytolytic approach to cancer therapy using a fusion protein consisting of Cltx and a ribosomal inactivating plant toxin, saporin, and test this approach in vitro and in animal tumor models of glioma and PNETs. PROPOSED COMMERCIAL APPLICATIONS: Cancer affects one-third of the US population and is the second leading cause of death with 1.2 million new cases being diagnosed and over 500,000 people dying each year. The American Cancer Society reports that nearly 24,000 new cases of glioma and a much larger number of peripheral neuroectodermal tumors occur each year. Chemotherapy, radiation, and resction of tumors are the accepted methods of treatment. However, these methods provide little specificity for tumor tissue and recurrence is usually inevitable. There is a need to increase the time to progression, limit recurrence, externl survival, and improve the quality of life through the development of highly specific, targeted, efficacious treatments.
Funding Period: 2000-08-15 - 2001-07-31
more information: NIH RePORT